Skip to main content

Advertisement

SpringerLink
Log in

Binding between Prion Protein and Aβ Oligomers Contributes to the Pathogenesis of Alzheimer’s Disease

  • Review
  • Published:
Virologica Sinica

Abstract

A plethora of evidence suggests that protein misfolding and aggregation are underlying mechanisms of various neurodegenerative diseases, such as prion diseases and Alzheimer’s disease (AD). Like prion diseases, AD has been considered as an infectious disease in the past decades as it shows strain specificity and transmission potential. Although it remains elusive how protein aggregation leads to AD, it is becoming clear that cellular prion protein (PrPC) plays an important role in AD pathogenesis. Here, we briefly reviewed AD pathogenesis and focused on recent progresses how PrPC contributed to AD development. In addition, we proposed a potential mechanism to explain why infectious agents, such as viruses, conduce AD pathogenesis. Microbe infections cause Aβ deposition and upregulation of PrPC, which lead to high affinity binding between Aβ oligomers and PrPC. The interaction between PrPC and Aβ oligomers in turn activates the Fyn signaling cascade, resulting in neuron death in the central nervous system (CNS). Thus, silencing PrPC expression may turn out be an effective treatment for PrPC dependent AD.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6

Similar content being viewed by others

References

  • Alim MA, Hossain MS, Arima K, Takeda K, Izumiyama Y, Nakamura M, Kaji H, Shinoda T, Hisanaga S, Ueda K (2002) Tubulin seeds alpha-synuclein fibril formation. J Biol Chem 277:2112–2117

    CAS  PubMed  Google Scholar 

  • Allinson TM, Parkin ET, Turner AJ, Hooper NM (2003) ADAMs family members as amyloid precursor protein alpha-secretases. J Neurosci Res 74:342–352

    CAS  PubMed  Google Scholar 

  • Alonso AD, Grundke-Iqbal I, Barra HS, Iqbal K (1997) Abnormal phosphorylation of tau and the mechanism of Alzheimer neurofibrillary degeneration: sequestration of microtubule-associated proteins 1 and 2 and the disassembly of microtubules by the abnormal tau. Proc Natl Acad Sci USA 94:298–303

    CAS  PubMed  PubMed Central  Google Scholar 

  • Armstrong RA, Lantos PL, Cairns NJ (2005) Overlap between neurodegenerative disorders. Neuropathology 25:111–124

    PubMed  Google Scholar 

  • Balducci C, Beeg M, Stravalaci M, Bastone A, Sclip A, Biasini E, Tapella L, Colombo L, Manzoni C, Borsello T, Chiesa R, Gobbi M, Salmona M, Forloni G (2010) Synthetic amyloid-beta oligomers impair long-term memory independently of cellular prion protein. Proc Natl Acad Sci USA 107:2295–2300

    CAS  PubMed  PubMed Central  Google Scholar 

  • Balin BJ, Gerard HC, Arking EJ, Appelt DM, Branigan PJ, Abrams JT, Whittum-Hudson JA, Hudson AP (1998) Identification and localization of Chlamydia pneumoniae in the Alzheimer’s brain. Med Microbiol Immunol 187:23–42

    CAS  PubMed  Google Scholar 

  • Ball MJ (1980) Features of Creutzfeldt–Jakob disease in brains of patients with familial dementia of Alzheimer type. Can J Neurol Sci 7:51–57

    CAS  PubMed  Google Scholar 

  • Ballard C, Gauthier S, Corbett A, Brayne C, Aarsland D, Jones E (2011) Alzheimer’s disease. Lancet 377:1019–1031

    PubMed  Google Scholar 

  • Ballatore C, Lee VM, Trojanowski JQ (2007) Tau-mediated neurodegeneration in Alzheimer’s disease and related disorders. Nat Rev Neurosci 8:663–672

    CAS  PubMed  Google Scholar 

  • Banks WA, Niehoff ML, Drago D, Zatta P (2006) Aluminum complexing enhances amyloid beta protein penetration of blood–brain barrier. Brain Res 1116:215–221

    CAS  PubMed  Google Scholar 

  • Barry AE, Klyubin I, Mc Donald JM, Mably AJ, Farrell MA, Scott M, Walsh DM, Rowan MJ (2011) Alzheimer’s disease brain-derived amyloid-beta-mediated inhibition of LTP in vivo is prevented by immunotargeting cellular prion protein. J Neurosci 31:7259–7263

    CAS  PubMed  PubMed Central  Google Scholar 

  • Basler K, Oesch B, Scott M, Westaway D, Walchli M, Groth DF, McKinley MP, Prusiner SB, Weissmann C (1986) Scrapie and cellular PrP isoforms are encoded by the same chromosomal gene. Cell 46:417–428

    CAS  PubMed  Google Scholar 

  • Bate C, Williams A (2011) Amyloid-beta-induced synapse damage is mediated via cross-linkage of cellular prion proteins. J Biol Chem 286:37955–37963

    CAS  PubMed  PubMed Central  Google Scholar 

  • Bateman RJ, Aisen PS, De Strooper B, Fox NC, Lemere CA, Ringman JM, Salloway S, Sperling RA, Windisch M, Xiong C (2011) Autosomal-dominant Alzheimer’s disease: a review and proposal for the prevention of Alzheimer’s disease. Alzheimers Res Ther 3:1

    PubMed  PubMed Central  Google Scholar 

  • Bekris LM, Yu CE, Bird TD, Tsuang DW (2010) Genetics of Alzheimer disease. J Geriatr Psychiatry Neurol 23:213–227

    PubMed  PubMed Central  Google Scholar 

  • Bertram L, McQueen MB, Mullin K, Blacker D, Tanzi RE (2007) Systematic meta-analyses of Alzheimer disease genetic association studies: the AlzGene database. Nat Genet 39:17–23

    CAS  PubMed  Google Scholar 

  • Beyer K (2006) Alpha-synuclein structure, posttranslational modification and alternative splicing as aggregation enhancers. Acta Neuropathol 112:237–251

    CAS  PubMed  Google Scholar 

  • Bi R, Zhang W, Zhang DF, Xu M, Fan Y, Hu QX, Jiang HY, Tan L, Li T, Fang Y, Zhang C, Yao YG (2018) Genetic association of the cytochrome c oxidase-related genes with Alzheimer’s disease in Han Chinese. Neuropsychopharmacology 43:2264–2276

    CAS  PubMed  PubMed Central  Google Scholar 

  • Billingsley ML, Kincaid RL (1997) Regulated phosphorylation and dephosphorylation of tau protein: effects on microtubule interaction, intracellular trafficking and neurodegeneration. Biochem J 323:577–591

    CAS  PubMed  PubMed Central  Google Scholar 

  • Bird TD (2008) Genetic aspects of Alzheimer disease. Genet Med 10:231–239

    CAS  PubMed  PubMed Central  Google Scholar 

  • Blennow K, de Leon MJ, Zetterberg H (2006) Alzheimer’s disease. Lancet 368:387–403

    CAS  PubMed  Google Scholar 

  • Bolognin S, Messori L, Drago D, Gabbiani C, Cendron L, Zatta P (2011) Aluminum, copper, iron and zinc differentially alter amyloid-Abeta(1-42) aggregation and toxicity. Int J Biochem Cell Biol 43:877–885

    CAS  PubMed  Google Scholar 

  • Brickell KL, Steinbart EJ, Rumbaugh M, Payami H, Schellenberg GD, Van Deerlin V, Yuan W, Bird TD (2006) Early-onset Alzheimer disease in families with late-onset Alzheimer disease: a potential important subtype of familial Alzheimer disease. Arch Neurol 63:1307–1311

    PubMed  Google Scholar 

  • Brown P, Salazar AM, Gibbs CJ Jr, Gajdusek DC (1982) Alzheimer’s disease and transmissible virus dementia (Creutzfeldt–Jakob disease). Ann N Y Acad Sci 396:131–143

    CAS  PubMed  Google Scholar 

  • Buee L, Bussiere T, Buee-Scherrer V, Delacourte A, Hof PR (2000) Tau protein isoforms, phosphorylation and role in neurodegenerative disorders. Brain Res Brain Res Rev 33:95–130

    CAS  PubMed  Google Scholar 

  • Burre J, Sharma M, Sudhof TC (2012) Systematic mutagenesis of alpha-synuclein reveals distinct sequence requirements for physiological and pathological activities. J Neurosci 32:15227–15242

    CAS  PubMed  PubMed Central  Google Scholar 

  • Calella AM, Farinelli M, Nuvolone M, Mirante O, Moos R, Falsig J, Mansuy IM, Aguzzi A (2010) Prion protein and Abeta-related synaptic toxicity impairment. EMBO Mol Med 2:306–314

    CAS  PubMed  PubMed Central  Google Scholar 

  • Campion D, Dumanchin C, Hannequin D, Dubois B, Belliard S, Puel M, Thomas-Anterion C, Michon A, Martin C, Charbonnier F, Raux G, Camuzat A, Penet C, Mesnage V, Martinez M, Clerget-Darpoux F, Brice A, Frebourg T (1999) Early-onset autosomal dominant Alzheimer disease: prevalence, genetic heterogeneity, and mutation spectrum. Am J Hum Genet 65:664–670

    CAS  PubMed  PubMed Central  Google Scholar 

  • Carbone I, Lazzarotto T, Ianni M, Porcellini E, Forti P, Masliah E, Gabrielli L, Licastro F (2014) Herpes virus in Alzheimer’s disease: relation to progression of the disease. Neurobiol Aging 35:122–129

    PubMed  Google Scholar 

  • Carrasquillo MM, Belbin O, Hunter TA, Ma L, Bisceglio GD, Zou F, Crook JE, Pankratz VS, Dickson DW, Graff-Radford NR, Petersen RC, Morgan K, Younkin SG (2010) Replication of CLU, CR30, and PICALM associations with alzheimer disease. Arch Neurol 67:961–964

    PubMed  PubMed Central  Google Scholar 

  • Castillo GM, Lukito W, Wight TN, Snow AD (1999) The sulfate moieties of glycosaminoglycans are critical for the enhancement of beta-amyloid protein fibril formation. J Neurochem 72:1681–1687

    CAS  PubMed  Google Scholar 

  • Cataldo JK, Prochaska JJ, Glantz SA (2010) Cigarette smoking is a risk factor for Alzheimer’s disease: an analysis controlling for tobacco industry affiliation. J Alzheimers Dis 19:465–480

    PubMed  PubMed Central  Google Scholar 

  • Chandra S, Chen X, Rizo J, Jahn R, Sudhof TC (2003) A broken alpha-helix in folded alpha-Synuclein. J Biol Chem 278:15313–15318

    CAS  PubMed  Google Scholar 

  • Chandra S, Gallardo G, Fernandez-Chacon R, Schluter OM, Sudhof TC (2005) Alpha-synuclein cooperates with CSPalpha in preventing neurodegeneration. Cell 123:383–396

    CAS  PubMed  Google Scholar 

  • Chen S, Yadav SP, Surewicz WK (2010) Interaction between human prion protein and amyloid-beta (Abeta) oligomers: role OF N-terminal residues. J Biol Chem 285:26377–26383

    CAS  PubMed  PubMed Central  Google Scholar 

  • Chene G, Beiser A, Au R, Preis SR, Wolf PA, Dufouil C, Seshadri S (2015) Gender and incidence of dementia in the Framingham Heart Study from mid-adult life. Alzheimers Dement 11:310–320

    PubMed  Google Scholar 

  • Chin J, Palop JJ, Puolivali J, Massaro C, Bien-Ly N, Gerstein H, Scearce-Levie K, Masliah E, Mucke L (2005) Fyn kinase induces synaptic and cognitive impairments in a transgenic mouse model of Alzheimer’s disease. J Neurosci 25:9694–9703

    CAS  PubMed  PubMed Central  Google Scholar 

  • Chouraki V, Seshadri S (2014) Genetics of Alzheimer’s disease. Adv Genet 87:245–294

    CAS  PubMed  Google Scholar 

  • Chung E, Ji Y, Sun Y, Kascsak RJ, Kascsak RB, Mehta PD, Strittmatter SM, Wisniewski T (2010) Anti-PrPC monoclonal antibody infusion as a novel treatment for cognitive deficits in an Alzheimer’s disease model mouse. BMC Neurosci 11:130

    PubMed  PubMed Central  Google Scholar 

  • Clayton DF, George JM (1998) The synucleins: a family of proteins involved in synaptic function, plasticity, neurodegeneration and disease. Trends Neurosci 21:249–254

    CAS  PubMed  Google Scholar 

  • Cleobury JF, Skinner GR, Thouless ME, Wildy P (1971) Association between psychopathic disorder and serum antibody to herpes simplex virus (type 1). Br Med J 1:438–439

    CAS  PubMed  PubMed Central  Google Scholar 

  • Cleveland DW, Hwo SY, Kirschner MW (1977) Purification of tau, a microtubule-associated protein that induces assembly of microtubules from purified tubulin. J Mol Biol 116:207–225

    CAS  PubMed  Google Scholar 

  • Cook RH, Austin JH (1978) Precautions in familial transmissible dementia: including familial Alzheimer’s disease. Arch Neurol 35:697–698

    CAS  PubMed  Google Scholar 

  • Cooke SF, Bliss TV (2006) Plasticity in the human central nervous system. Brain 129:1659–1673

    CAS  PubMed  Google Scholar 

  • Corder E, Lannfelt L, Mulder M (1998) Apolipoprotein E and herpes simplex virus 1 in Alzheimer’s disease. Lancet 352:1312–1313

    CAS  PubMed  Google Scholar 

  • Corneveaux JJ, Myers AJ, Allen AN, Pruzin JJ, Ramirez M, Engel A, Nalls MA, Chen K, Lee W, Chewning K, Villa SE, Meechoovet HB, Gerber JD, Frost D, Benson HL, O’Reilly S, Chibnik LB, Shulman JM, Singleton AB, Craig DW, Van Keuren-Jensen KR, Dunckley T, Bennett DA, De Jager PL, Heward C, Hardy J, Reiman EM, Huentelman MJ (2010) Association of CR46, CLU and PICALM with Alzheimer’s disease in a cohort of clinically characterized and neuropathologically verified individuals. Hum Mol Genet 19:3295–3301

    CAS  PubMed  PubMed Central  Google Scholar 

  • de Almeida CJ, Chiarini LB, da Silva JP, E Silva PM, Martins MA, Linden R (2005) The cellular prion protein modulates phagocytosis and inflammatory response. J Leukoc Biol 77:238–246

    PubMed  Google Scholar 

  • De Mario A, Castellani A, Peggion C, Massimino ML, Lim D, Hill AF, Sorgato MC, Bertoli A (2015) The prion protein constitutively controls neuronal store-operated Ca2+ entry through Fyn kinase. Front Cell Neurosci 9:416

    PubMed  PubMed Central  Google Scholar 

  • Denaro FJ, Staub P, Colmer J, Freed DM (2003) Coexistence of Alzheimer disease neuropathology with herpes simplex encephalitis. Cell Mol Biol (Noisy-le-grand) 49:1233–1240

    CAS  Google Scholar 

  • Ding T, Zhou X, Kouadir M, Shi F, Yang Y, Liu J, Wang M, Yin X, Yang L, Zhao D (2013) Cellular prion protein participates in the regulation of inflammatory response and apoptosis in BV2 microglia during infection with Mycobacterium bovis. J Mol Neurosci 51:118–126

    CAS  PubMed  Google Scholar 

  • Dittrich W, Bode L, Ludwig H, Kao M, Schneider K (1989) Learning deficiencies in Borna disease virus-infected but clinically healthy rats. Biol Psychiatry 26:818–828

    CAS  PubMed  Google Scholar 

  • Dohler F, Sepulveda-Falla D, Krasemann S, Altmeppen H, Schluter H, Hildebrand D, Zerr I, Matschke J, Glatzel M (2014) High molecular mass assemblies of amyloid-beta oligomers bind prion protein in patients with Alzheimer’s disease. Brain 137:873–886

    PubMed  Google Scholar 

  • Dominy SS, Lynch C, Ermini F, Benedyk M, Marczyk A, Konradi A, Nguyen M, Haditsch U, Raha D, Griffin C, Holsinger LJ, Arastu-Kapur S, Kaba S, Lee A, Ryder MI, Potempa B, Mydel P, Hellvard A, Adamowicz K, Hasturk H, Walker GD, Reynolds EC, Faull RLM, Curtis MA, Dragunow M, Potempa J (2019) Porphyromonas gingivalis in Alzheimer’s disease brains: evidence for disease causation and treatment with small-molecule inhibitors. Sci Adv 5:eaau3333

    PubMed  PubMed Central  Google Scholar 

  • Edbauer D, Winkler E, Regula JT, Pesold B, Steiner H, Haass C (2003) Reconstitution of gamma-secretase activity. Nat Cell Biol 5:486–488

    CAS  PubMed  Google Scholar 

  • El Bitar F, Qadi N, Al Rajeh S, Majrashi A, Abdulaziz S, Majrashi N, Al Inizi M, Taher A, Al Tassan N (2019) Genetic study of Alzheimer’s disease in Saudi population. J Alzheimers Dis 67:231–242

    PubMed  Google Scholar 

  • Falker C, Hartmann A, Guett I, Dohler F, Altmeppen H, Betzel C, Schubert R, Thurm D, Wegwitz F, Joshi P, Verderio C, Krasemann S, Glatzel M (2016) Exosomal cellular prion protein drives fibrillization of amyloid beta and counteracts amyloid beta-mediated neurotoxicity. J Neurochem 137:88–100

    CAS  PubMed  Google Scholar 

  • Fluharty BR, Biasini E, Stravalaci M, Sclip A, Diomede L, Balducci C, La Vitola P, Messa M, Colombo L, Forloni G, Borsello T, Gobbi M, Harris DA (2013) An N-terminal fragment of the prion protein binds to amyloid-beta oligomers and inhibits their neurotoxicity in vivo. J Biol Chem 288:7857–7866

    CAS  PubMed  PubMed Central  Google Scholar 

  • Gajdusek DC (1994) Spontaneous generation of infectious nucleating amyloids in the transmissible and nontransmissible cerebral amyloidoses. Mol Neurobiol 8:1–13

    CAS  PubMed  Google Scholar 

  • Ganzinger KA, Narayan P, Qamar SS, Weimann L, Ranasinghe RT, Aguzzi A, Dobson CM, McColl J, St George-Hyslop P, Klenerman D (2014) Single-molecule imaging reveals that small amyloid-beta1-42 oligomers interact with the cellular prion protein (PrP(C)). ChemBioChem 15:2515–2521

    CAS  PubMed  PubMed Central  Google Scholar 

  • Gao Z, Zhang H, Hu F, Yang L, Yang X, Zhu Y, Sy MS, Li C (2016) Glycan-deficient PrP stimulates VEGFR2 signaling via glycosaminoglycan. Cell Signal 28:652–662

    CAS  PubMed  Google Scholar 

  • Gao Z, Shi J, Cai L, Luo M, Wong BS, Dong X, Sy MS, Li C (2019) Prion dimer is heterogenous and is modulated by multiple negative and positive motifs. Biochem Biophys Res Commun 509:570–576

    CAS  PubMed  Google Scholar 

  • George JM, Jin H, Woods WS, Clayton DF (1995) Characterization of a novel protein regulated during the critical period for song learning in the zebra finch. Neuron 15:361–372

    CAS  PubMed  Google Scholar 

  • Ghetti B, Piccardo P, Spillantini MG, Ichimiya Y, Porro M, Perini F, Kitamoto T, Tateishi J, Seiler C, Frangione B, Bugiani O, Giaccone G, Prelli F, Goedert M, Dlouhy SR, Tagliavini F (1996) Vascular variant of prion protein cerebral amyloidosis with tau-positive neurofibrillary tangles: the phenotype of the stop codon 145 mutation in PRNP. Proc Natl Acad Sci USA 93:744–748

    CAS  PubMed  PubMed Central  Google Scholar 

  • Gimbel DA, Nygaard HB, Coffey EE, Gunther EC, Lauren J, Gimbel ZA, Strittmatter SM (2010) Memory impairment in transgenic Alzheimer mice requires cellular prion protein. J Neurosci 30:6367–6374

    CAS  PubMed  PubMed Central  Google Scholar 

  • Glenner GG, Wong CW (1984) Alzheimer’s disease: initial report of the purification and characterization of a novel cerebrovascular amyloid protein. Biochem Biophys Res Commun 120:885–890

    CAS  PubMed  Google Scholar 

  • Goedert M, Wischik CM, Crowther RA, Walker JE, Klug A (1988) Cloning and sequencing of the cDNA encoding a core protein of the paired helical filament of Alzheimer disease: identification as the microtubule-associated protein tau. Proc Natl Acad Sci USA 85:4051–4055

    CAS  PubMed  PubMed Central  Google Scholar 

  • Goedert M, Spillantini MG, Jakes R, Rutherford D, Crowther RA (1989) Multiple isoforms of human microtubule-associated protein tau: sequences and localization in neurofibrillary tangles of Alzheimer’s disease. Neuron 3:519–526

    CAS  PubMed  Google Scholar 

  • Goldman JS, Hahn SE, Catania JW, Larusse-Eckert S, Butson MB, Rumbaugh M, Strecker MN, Roberts JS, Burke W, Mayeux R, Bird T (2011) Genetic counseling and testing for Alzheimer disease: joint practice guidelines of the American College of Medical Genetics and the National Society of Genetic Counselors. Genet Med 13:597

    PubMed  PubMed Central  Google Scholar 

  • Gonsalves D, Jovanovic K, Da Costa Dias B, Weiss SF (2012) Global Alzheimer Research Summit: basic and clinical research: present and future Alzheimer research. Prion 6:7–10

    PubMed  PubMed Central  Google Scholar 

  • Gotz J, Chen F, van Dorpe J, Nitsch RM (2001) Formation of neurofibrillary tangles in P301l tau transgenic mice induced by Abeta 42 fibrils. Science 293:1491–1495

    CAS  PubMed  Google Scholar 

  • Gourdain P, Ballerini C, Nicot AB, Carnaud C (2012) Exacerbation of experimental autoimmune encephalomyelitis in prion protein (PrPc)-null mice: evidence for a critical role of the central nervous system. J Neuroinflamm 9:25

    CAS  Google Scholar 

  • Guo JL, Covell DJ, Daniels JP, Iba M, Stieber A, Zhang B, Riddle DM, Kwong LK, Xu Y, Trojanowski JQ, Lee VM (2013) Distinct alpha-synuclein strains differentially promote tau inclusions in neurons. Cell 154:103–117

    CAS  PubMed  Google Scholar 

  • Haas LT, Kostylev MA, Strittmatter SM (2014) Therapeutic molecules and endogenous ligands regulate the interaction between brain cellular prion protein (PrPC) and metabotropic glutamate receptor 5 (mGluR5). J Biol Chem 289:28460–28477

    CAS  PubMed  PubMed Central  Google Scholar 

  • Hebert LE, Scherr PA, McCann JJ, Beckett LA, Evans DA (2001) Is the risk of developing Alzheimer’s disease greater for women than for men? Am J Epidemiol 153:132–136

    CAS  PubMed  Google Scholar 

  • Hebert LE, Weuve J, Scherr PA, Evans DA (2013) Alzheimer disease in the United States (2010–2050) estimated using the 2010 census. Neurology 80:1778–1783

    PubMed  PubMed Central  Google Scholar 

  • Himmelhoch E, Latham O, Mc DC (1947) Alzheimer’s disease complicated by a terminal salmonella infection. Med J Aust 1:701–703

    CAS  PubMed  Google Scholar 

  • Holtzman DM, Herz J, Bu G (2012) Apolipoprotein E and apolipoprotein E receptors: normal biology and roles in Alzheimer disease. Cold Spring Harb Perspect Med 2:a006312

    PubMed  PubMed Central  Google Scholar 

  • Hooli BV, Mohapatra G, Mattheisen M, Parrado AR, Roehr JT, Shen Y, Gusella JF, Moir R, Saunders AJ, Lange C, Tanzi RE, Bertram L (2012) Role of common and rare APP DNA sequence variants in Alzheimer disease. Neurology 78:1250–1257

    CAS  PubMed  PubMed Central  Google Scholar 

  • Hu W, Nessler S, Hemmer B, Eagar TN, Kane LP, Leliveld SR, Muller-Schiffmann A, Gocke AR, Lovett-Racke A, Ben LH, Hussain RZ, Breil A, Elliott JL, Puttaparthi K, Cravens PD, Singh MP, Petsch B, Stitz L, Racke MK, Korth C, Stuve O (2010) Pharmacological prion protein silencing accelerates central nervous system autoimmune disease via T cell receptor signalling. Brain 133:375–388

    PubMed  PubMed Central  Google Scholar 

  • Iqbal K, Alonso Adel C, Chen S, Chohan MO, El-Akkad E, Gong CX, Khatoon S, Li B, Liu F, Rahman A, Tanimukai H, Grundke-Iqbal I (2005) Tau pathology in Alzheimer disease and other tauopathies. Biochim Biophys Acta 1739:198–210

    CAS  PubMed  Google Scholar 

  • Itzhaki RF (2017) Herpes simplex virus type 1 and Alzheimer’s disease: possible mechanisms and signposts. Faseb j 31:3216–3226

    CAS  PubMed  Google Scholar 

  • Itzhaki RF, Lin WR, Shang D, Wilcock GK, Faragher B, Jamieson GA (1997) Herpes simplex virus type 1 in brain and risk of Alzheimer’s disease. Lancet 349:241–244

    CAS  PubMed  Google Scholar 

  • Iwai A, Masliah E, Yoshimoto M, Ge N, Flanagan L, de Silva HA, Kittel A, Saitoh T (1995) The precursor protein of non-A beta component of Alzheimer’s disease amyloid is a presynaptic protein of the central nervous system. Neuron 14:467–475

    CAS  PubMed  Google Scholar 

  • Jack CR Jr, Knopman DS, Jagust WJ, Shaw LM, Aisen PS, Weiner MW, Petersen RC, Trojanowski JQ (2010) Hypothetical model of dynamic biomarkers of the Alzheimer’s pathological cascade. Lancet Neurol 9:119–128

    CAS  PubMed  PubMed Central  Google Scholar 

  • Jamieson GA, Maitland NJ, Wilcock GK, Craske J, Itzhaki RF (1991) Latent herpes simplex virus type 1 in normal and Alzheimer’s disease brains. J Med Virol 33:224–227

    CAS  PubMed  Google Scholar 

  • Jamieson GA, Maitland NJ, Wilcock GK, Yates CM, Itzhaki RF (1992) Herpes simplex virus type 1 DNA is present in specific regions of brain from aged people with and without senile dementia of the Alzheimer type. J Pathol 167:365–368

    CAS  PubMed  Google Scholar 

  • Jellinger KA, Attems J (2010) Prevalence of dementia disorders in the oldest-old: an autopsy study. Acta Neuropathol 119:421–433

    PubMed  Google Scholar 

  • Jones EM, Surewicz WK (2005) Fibril conformation as the basis of species-and strain-dependent seeding specificity of mammalian prion amyloids. Cell 121:63–72

    CAS  PubMed  Google Scholar 

  • Kane MD, Lipinski WJ, Callahan MJ, Bian F, Durham RA, Schwarz RD, Roher AE, Walker LC (2000) Evidence for seeding of beta-amyloid by intracerebral infusion of Alzheimer brain extracts in beta-amyloid precursor protein-transgenic mice. J Neurosci 20:3606–3611

    CAS  PubMed  PubMed Central  Google Scholar 

  • Kim J (1997) Evidence that the precursor protein of non-A beta component of Alzheimer’s disease amyloid (NACP) has an extended structure primarily composed of random-coil. Mol Cells 7:78–83

    CAS  PubMed  Google Scholar 

  • Kivipelto M, Ngandu T, Laatikainen T, Winblad B, Soininen H, Tuomilehto J (2006) Risk score for the prediction of dementia risk in 20 years among middle aged people: a longitudinal, population-based study. Lancet Neurol 5:735–741

    PubMed  Google Scholar 

  • Konturek PC, Bazela K, Kukharskyy V, Bauer M, Hahn EG, Schuppan D (2005) Helicobacter pylori upregulates prion protein expression in gastric mucosa: a possible link to prion disease. World J Gastroenterol 11:7651–7656

    CAS  PubMed  PubMed Central  Google Scholar 

  • Kopke E, Tung YC, Shaikh S, Alonso AC, Iqbal K, Grundke-Iqbal I (1993) Microtubule-associated protein tau. Abnormal phosphorylation of a non-paired helical filament pool in Alzheimer disease. J Biol Chem 268:24374–24384

    CAS  PubMed  Google Scholar 

  • Kostylev MA, Kaufman AC, Nygaard HB, Patel P, Haas LT, Gunther EC, Vortmeyer A, Strittmatter SM (2015) Prion-protein-interacting Amyloid-beta oligomers of high molecular weight are tightly correlated with memory impairment in multiple Alzheimer mouse models. J Biol Chem 290:17415–17438

    CAS  PubMed  PubMed Central  Google Scholar 

  • Kountouras J, Tsolaki M, Gavalas E, Boziki M, Zavos C, Karatzoglou P, Chatzopoulos D, Venizelos I (2006) Relationship between Helicobacter pylori infection and Alzheimer disease. Neurology 66:938–940

    CAS  PubMed  Google Scholar 

  • Kovacs GG, Trabattoni G, Hainfellner JA, Ironside JW, Knight RS, Budka H (2002) Mutations of the prion protein gene phenotypic spectrum. J Neurol 249:1567–1582

    CAS  PubMed  Google Scholar 

  • Kruger J, Moilanen V, Majamaa K, Remes AM (2012) Molecular genetic analysis of the APP, PSEN1, and PSEN2 genes in Finnish patients with early-onset Alzheimer disease and frontotemporal lobar degeneration. Alzheimer Dis Assoc Disord 26:272–276

    CAS  PubMed  Google Scholar 

  • Kumar S, Rezaei-Ghaleh N, Terwel D, Thal DR, Richard M, Hoch M, Mc Donald JM, Wullner U, Glebov K, Heneka MT, Walsh DM, Zweckstetter M, Walter J (2011) Extracellular phosphorylation of the amyloid beta-peptide promotes formation of toxic aggregates during the pathogenesis of Alzheimer’s disease. EMBO J 30:2255–2265

    CAS  PubMed  PubMed Central  Google Scholar 

  • Lambert JC, Ibrahim-Verbaas CA, Harold D, Naj AC, Sims R, Bellenguez C, DeStafano AL, Bis JC, Beecham GW, Grenier-Boley B et al (2013) Meta-analysis of 74,046 individuals identifies 11 new susceptibility loci for Alzheimer’s disease. Nat Genet 45:1452–1458

    CAS  PubMed  PubMed Central  Google Scholar 

  • Lane CA, Hardy J, Schott JM (2018) Alzheimer’s disease. Eur J Neurol 25:59–70

    CAS  PubMed  Google Scholar 

  • Larson M, Sherman MA, Amar F, Nuvolone M, Schneider JA, Bennett DA, Aguzzi A, Lesne SE (2012) The complex PrP(c)-Fyn couples human oligomeric Abeta with pathological tau changes in Alzheimer’s disease. J Neurosci 32:16857–16871a

    CAS  PubMed  PubMed Central  Google Scholar 

  • Lauren J, Gimbel DA, Nygaard HB, Gilbert JW, Strittmatter SM (2009) Cellular prion protein mediates impairment of synaptic plasticity by amyloid-beta oligomers. Nature 457:1128–1132

    CAS  PubMed  PubMed Central  Google Scholar 

  • Lee VM, Balin BJ, Otvos L Jr, Trojanowski JQ (1991) A68: a major subunit of paired helical filaments and derivatized forms of normal Tau. Science 251:675–678

    CAS  PubMed  Google Scholar 

  • Lee HJ, Choi C, Lee SJ (2002) Membrane-bound alpha-synuclein has a high aggregation propensity and the ability to seed the aggregation of the cytosolic form. J Biol Chem 277:671–678

    CAS  PubMed  Google Scholar 

  • Lin WR, Wozniak MA, Cooper RJ, Wilcock GK, Itzhaki RF (2002) Herpesviruses in brain and Alzheimer’s disease. J Pathol 197:395–402

    CAS  PubMed  Google Scholar 

  • Liu J, Zhao D, Liu C, Ding T, Yang L, Yin X, Zhou X (2015) Prion protein participates in the protection of mice from lipopolysaccharide infection by regulating the inflammatory process. J Mol Neurosci 55:279–287

    CAS  PubMed  Google Scholar 

  • Lovheim H, Gilthorpe J, Adolfsson R, Nilsson LG, Elgh F (2015) Reactivated herpes simplex infection increases the risk of Alzheimer’s disease. Alzheimers Dement 11:593–599

    PubMed  Google Scholar 

  • Loy CT, Schofield PR, Turner AM, Kwok JB (2014) Genetics of dementia. Lancet 383:828–840

    CAS  PubMed  Google Scholar 

  • Luterman JD, Haroutunian V, Yemul S, Ho L, Purohit D, Aisen PS, Mohs R, Pasinetti GM (2000) Cytokine gene expression as a function of the clinical progression of Alzheimer disease dementia. Arch Neurol 57:1153–1160

    CAS  PubMed  Google Scholar 

  • Lycke E, Norrby R, Roos BE (1974) A serological study on mentally ill patients with particular reference to the prevalence of herpes virus infections. Br J Psychiatry 124:273–279

    CAS  PubMed  Google Scholar 

  • Mahley RW, Rall SC Jr (2000) Apolipoprotein E: far more than a lipid transport protein. Annu Rev Genom Hum Genet 1:507–537

    CAS  Google Scholar 

  • Markesbery W, Ehmann W (1993) Aluminum and Alzheimer’s disease. Clin Neurosci 1:212–218

    Google Scholar 

  • Maroteaux L, Campanelli JT, Scheller RH (1988) Synuclein: a neuron-specific protein localized to the nucleus and presynaptic nerve terminal. J Neurosci 8:2804–2815

    CAS  PubMed  PubMed Central  Google Scholar 

  • Martin L, Latypova X, Wilson CM, Magnaudeix A, Perrin ML, Yardin C, Terro F (2013) Tau protein kinases: involvement in Alzheimer’s disease. Ageing Res Rev 12:289–309

    CAS  PubMed  Google Scholar 

  • Masters CL, Gajdusek DC, Gibbs CJ Jr (1981) The familial occurrence of Creutzfeldt–Jakob disease and Alzheimer’s disease. Brain 104:535–558

    CAS  PubMed  Google Scholar 

  • Masters CL, Simms G, Weinman NA, Multhaup G, McDonald BL, Beyreuther K (1985) Amyloid plaque core protein in Alzheimer disease and Down syndrome. Proc Natl Acad Sci USA 82:4245–4249

    CAS  PubMed  PubMed Central  Google Scholar 

  • Matsuo ES, Shin RW, Billingsley ML, Van deVoorde A, O’Connor M, Trojanowski JQ, Lee VM (1994) Biopsy-derived adult human brain tau is phosphorylated at many of the same sites as Alzheimer’s disease paired helical filament tau. Neuron 13:989–1002

    CAS  PubMed  Google Scholar 

  • Mattsson N, Zetterberg H, Hansson O, Andreasen N, Parnetti L, Jonsson M, Herukka SK, van der Flier WM, Blankenstein MA, Ewers M, Rich K, Kaiser E, Verbeek M, Tsolaki M, Mulugeta E, Rosen E, Aarsland D, Visser PJ, Schroder J, Marcusson J, de Leon M, Hampel H, Scheltens P, Pirttila T, Wallin A, Jonhagen ME, Minthon L, Winblad B, Blennow K (2009) CSF biomarkers and incipient Alzheimer disease in patients with mild cognitive impairment. JAMA 302:385–393

    CAS  PubMed  Google Scholar 

  • Maurer K, Volk S, Gerbaldo H (1997) Auguste D and Alzheimer’s disease. Lancet 349:1546–1549

    CAS  PubMed  Google Scholar 

  • McLachlan DR, Fraser PE, Dalton AJ (1992) Aluminium and the pathogenesis of Alzheimer's disease: a summary of evidence. Ciba Found Symp 169:87–98

    CAS  PubMed  Google Scholar 

  • McLean PJ, Kawamata H, Ribich S, Hyman BT (2000) Membrane association and protein conformation of alpha-synuclein in intact neurons. Effect of Parkinson’s disease-linked mutations. J Biol Chem 275:8812–8816

    CAS  PubMed  Google Scholar 

  • McNamara J, Murray TA (2016) Connections between herpes simplex virus type 1 and Alzheimer’s disease pathogenesis. Curr Alzheimer Res 13:996–1005

    CAS  PubMed  Google Scholar 

  • Meyer-Luehmann M, Coomaraswamy J, Bolmont T, Kaeser S, Schaefer C, Kilger E, Neuenschwander A, Abramowski D, Frey P, Jaton AL, Vigouret JM, Paganetti P, Walsh DM, Mathews PM, Ghiso J, Staufenbiel M, Walker LC, Jucker M (2006) Exogenous induction of cerebral beta-amyloidogenesis is governed by agent and host. Science 313:1781–1784

    CAS  PubMed  Google Scholar 

  • Middleton PJ, Petric M, Kozak M, Rewcastle NB, McLachlan DR (1980) Herpes-simplex viral genome and senile and presenile dementias of Alzheimer and Pick. Lancet 1:1038

    CAS  PubMed  Google Scholar 

  • Mielke MM, Vemuri P, Rocca WA (2014) Clinical epidemiology of Alzheimer’s disease: assessing sex and gender differences. Clin Epidemiol 6:37–48

    PubMed  PubMed Central  Google Scholar 

  • Miklossy J (1993) Alzheimer’s disease—a spirochetosis? NeuroReport 4:841–848

    CAS  PubMed  Google Scholar 

  • Miklossy J, Kasas S, Janzer RC, Ardizzoni F, Van der Loos H (1994) Further ultrastructural evidence that spirochaetes may play a role in the aetiology of Alzheimer’s disease. NeuroReport 5:1201–1204

    CAS  PubMed  Google Scholar 

  • Miklossy J, Kis A, Radenovic A, Miller L, Forro L, Martins R, Reiss K, Darbinian N, Darekar P, Mihaly L, Khalili K (2006) Beta-amyloid deposition and Alzheimer’s type changes induced by Borrelia spirochetes. Neurobiol Aging 27:228–236

    CAS  PubMed  Google Scholar 

  • Mirra SS, Anand R, Spira TJ (1986) HTLV-III/LAV infection of the central nervous system in a 57-year-old man with progressive dementia of unknown cause. N Engl J Med 314:1191–1192

    CAS  PubMed  Google Scholar 

  • Mollinedo F, Gajate C (2015) Lipid rafts as major platforms for signaling regulation in cancer. Adv Biol Regul 57:130–146

    CAS  PubMed  Google Scholar 

  • Moulton PV, Yang W (2012) Air pollution, oxidative stress, and Alzheimer’s disease. J Environ Public Health 2012:472751

    PubMed  PubMed Central  Google Scholar 

  • Mozar HN, Bal DG, Howard JT (1987) Perspectives on the etiology of Alzheimer’s disease. JAMA 257:1503–1507

    CAS  PubMed  Google Scholar 

  • Mukherjee S, Mez J, Trittschuh EH, Saykin AJ, Gibbons LE, Fardo DW, Wessels M, Bauman J, Moore M, Choi SE, Gross AL, Rich J, Louden DKN, Sanders RE, Grabowski TJ, Bird TD, McCurry SM, Snitz BE, Kamboh MI, Lopez OL, De Jager PL, Bennett DA, Keene CD, Larson EB, Crane PK (2018) Genetic data and cognitively defined late-onset Alzheimer’s disease subgroups. Mol Psychiatry. https://doi.org/10.1038/s41380-018-0298-8

    Article  PubMed  PubMed Central  Google Scholar 

  • Muller WE, Pfeifer K, Forrest J, Rytik PG, Eremin VF, Popov SA, Schroder HC (1992) Accumulation of transcripts coding for prion protein in human astrocytes during infection with human immunodeficiency virus. Biochim Biophys Acta 1139:32–40

    CAS  PubMed  Google Scholar 

  • Oshima M, Azuma H, Suzutani T, Ikeda H, Okuno A (2001) Direct and mononuclear cell mediated effects on interleukin 6 production by glioma cells in infection with herpes simplex virus type 1. J Med Virol 63:252–258

    CAS  PubMed  Google Scholar 

  • Ow SY, Dunstan DE (2014) A brief overview of amyloids and Alzheimer’s disease. Protein Sci 23:1315–1331

    CAS  PubMed  PubMed Central  Google Scholar 

  • Pammer J, Weninger W, Tschachler E (1998) Human keratinocytes express cellular prion-related protein in vitro and during inflammatory skin diseases. Am J Pathol 153:1353–1358

    CAS  PubMed  PubMed Central  Google Scholar 

  • Pan T, Wong BS, Liu T, Li R, Petersen RB, Sy MS (2002) Cell-surface prion protein interacts with glycosaminoglycans. Biochem J 368:81–90

    CAS  PubMed  PubMed Central  Google Scholar 

  • Pan T, Chang B, Wong P, Li C, Li R, Kang SC, Robinson JD, Thompsett AR, Tein P, Yin S, Barnard G, McConnell I, Brown DR, Wisniewski T, Sy MS (2005) An aggregation-specific enzyme-linked immunosorbent assay: detection of conformational differences between recombinant PrP protein dimers and PrP(Sc) aggregates. J Virol 79:12355–12364

    CAS  PubMed  PubMed Central  Google Scholar 

  • Pantera B, Bini C, Cirri P, Paoli P, Camici G, Manao G, Caselli A (2009) PrPc activation induces neurite outgrowth and differentiation in PC12 cells: role for caveolin-1 in the signal transduction pathway. J Neurochem 110:194–207

    CAS  PubMed  Google Scholar 

  • Petit CS, Barreau F, Besnier L, Gandille P, Riveau B, Chateau D, Roy M, Berrebi D, Svrcek M, Cardot P, Rousset M, Clair C, Thenet S (2012) Requirement of cellular prion protein for intestinal barrier function and mislocalization in patients with inflammatory bowel disease. Gastroenterology 143:122–132.e115

    CAS  PubMed  Google Scholar 

  • Petkova AT, Leapman RD, Guo Z, Yau WM, Mattson MP, Tycko R (2005) Self-propagating, molecular-level polymorphism in Alzheimer’s beta-amyloid fibrils. Science 307:262–265

    CAS  PubMed  Google Scholar 

  • Pohanka M (2018) Oxidative stress in Alzheimer disease as a target for therapy. Bratisl Lek Listy 119:535–543

    CAS  PubMed  Google Scholar 

  • Pratico D, Uryu K, Sung S, Tang S, Trojanowski JQ, Lee VM (2002) Aluminum modulates brain amyloidosis through oxidative stress in APP transgenic mice. Faseb j 16:1138–1140

    CAS  PubMed  Google Scholar 

  • Price JL, Ko AI, Wade MJ, Tsou SK, McKeel DW, Morris JC (2001) Neuron number in the entorhinal cortex and CA1 in preclinical Alzheimer disease. Arch Neurol 58:1395–1402

    CAS  PubMed  Google Scholar 

  • Priola SA, Caughey B, Wehrly K, Chesebro B (1995) A 60-kDa prion protein (PrP) with properties of both the normal and scrapie-associated forms of PrP. J Biol Chem 270:3299–3305

    CAS  PubMed  Google Scholar 

  • Prusiner SB (1998) Prions. Proc Natl Acad Sci USA 95:13363–13383

    CAS  PubMed  PubMed Central  Google Scholar 

  • Rambold AS, Muller V, Ron U, Ben-Tal N, Winklhofer KF, Tatzelt J (2008) Stress-protective signalling of prion protein is corrupted by scrapie prions. EMBO J 27:1974–1984

    CAS  PubMed  PubMed Central  Google Scholar 

  • Rao S, Ghani M, Guo Z, Deming Y, Wang K, Sims R, Mao C, Yao Y, Cruchaga C, Stephan DA, Rogaeva E (2018) An APOE-independent cis-eSNP on chromosome 19q13.32 influences tau levels and late-onset Alzheimer’s disease risk. Neurobiol Aging 66:178.e171–178.e178

    Google Scholar 

  • Readhead B, Haure-Mirande JV, Funk CC, Richards MA, Shannon P, Haroutunian V, Sano M, Liang WS, Beckmann ND, Price ND, Reiman EM, Schadt EE, Ehrlich ME, Gandy S, Dudley JT (2018) Multiscale analysis of independent Alzheimer’s Cohorts finds disruption of molecular, genetic, and clinical networks by human herpesvirus. Neuron 99:64–82.e67

    CAS  PubMed  PubMed Central  Google Scholar 

  • Reitz C, Mayeux R (2014) Alzheimer disease: epidemiology, diagnostic criteria, risk factors and biomarkers. Biochem Pharmacol 88:640–651

    CAS  PubMed  PubMed Central  Google Scholar 

  • Renvoize EB, Hambling MH (1984) Cytomegalovirus infection and Alzheimer’s disease. Age Ageing 13:205–209

    CAS  PubMed  Google Scholar 

  • Renvoize EB, Hambling MH, Pepper MD, Rajah SM (1979) Possible association of Alzheimer’s disease with HLA-BW15 and cytomegalovirus infection. Lancet 1:1238

    CAS  PubMed  Google Scholar 

  • Riviere GR, Riviere KH, Smith KS (2002) Molecular and immunological evidence of oral Treponema in the human brain and their association with Alzheimer’s disease. Oral Microbiol Immunol 17:113–118

    CAS  PubMed  Google Scholar 

  • Roses AD (2006) On the discovery of the genetic association of Apolipoprotein E genotypes and common late-onset Alzheimer disease. J Alzheimers Dis 9:361–366

    CAS  PubMed  Google Scholar 

  • Rushworth JV, Griffiths HH, Watt NT, Hooper NM (2013) Prion protein-mediated toxicity of amyloid-beta oligomers requires lipid rafts and the transmembrane LRP1. J Biol Chem 288:8935–8951

    CAS  PubMed  PubMed Central  Google Scholar 

  • Sakono M, Zako T (2010) Amyloid oligomers: formation and toxicity of Abeta oligomers. FEBS J 277:1348–1358

    CAS  PubMed  Google Scholar 

  • Sauder C, Wolfer DP, Lipp HP, Staeheli P, Hausmann J (2001) Learning deficits in mice with persistent Borna disease virus infection of the CNS associated with elevated chemokine expression. Behav Brain Res 120:189–201

    CAS  PubMed  Google Scholar 

  • Schatzl HM, Da Costa M, Taylor L, Cohen FE, Prusiner SB (1997) Prion protein gene variation among primates. J Mol Biol 265:257

    CAS  PubMed  Google Scholar 

  • Schott JM (2015) Infection, inflammation and Alzheimer’s disease. Eur J Neurol 22:1503–1504

    CAS  PubMed  Google Scholar 

  • Sequiera LW, Jennings LC, Carrasco LH, Lord MA, Curry A, Sutton RN (1979) Detection of herpes-simplex viral genome in brain tissue. Lancet 2:609–612

    CAS  PubMed  Google Scholar 

  • Serretti A, Artioli P, Quartesan R, De Ronchi D (2005) Genes involved in Alzheimer’s disease, a survey of possible candidates. J Alzheimers Dis 7:331–353

    CAS  PubMed  Google Scholar 

  • Seshadri S, Wolf PA, Beiser A, Au R, McNulty K, White R, D’Agostino RB (1997) Lifetime risk of dementia and Alzheimer’s disease. The impact of mortality on risk estimates in the Framingham Study. Neurology 49:1498–1504

    CAS  PubMed  Google Scholar 

  • Shankar GM, Li S, Mehta TH, Garcia-Munoz A, Shepardson NE, Smith I, Brett FM, Farrell MA, Rowan MJ, Lemere CA, Regan CM, Walsh DM, Sabatini BL, Selkoe DJ (2008) Amyloid-beta protein dimers isolated directly from Alzheimer’s brains impair synaptic plasticity and memory. Nat Med 14:837–842

    CAS  PubMed  PubMed Central  Google Scholar 

  • Shin RW, Lee VM, Trojanowski JQ (1995) Neurofibrillary pathology and aluminum in Alzheimer’s disease. Histol Histopathol 10:969–978

    CAS  PubMed  Google Scholar 

  • Simons K, Toomre D (2000) Lipid rafts and signal transduction. Nat Rev Mol Cell Biol 1:31–39

    CAS  PubMed  Google Scholar 

  • Sochocka M, Zwolinska K, Leszek J (2017) The infectious etiology of Alzheimer’s disease. Curr Neuropharmacol 15:996–1009

    CAS  PubMed  PubMed Central  Google Scholar 

  • Spillantini MG, Schmidt ML, Lee VM, Trojanowski JQ, Jakes R, Goedert M (1997) Alpha-synuclein in Lewy bodies. Nature 388:839–840

    CAS  PubMed  Google Scholar 

  • Spinney L (2014) Alzheimer’s disease: the forgetting gene. Nature 510:26–28

    CAS  PubMed  Google Scholar 

  • Sproul AA, Jacob S, Pre D, Kim SH, Nestor MW, Navarro-Sobrino M, Santa-Maria I, Zimmer M, Aubry S, Steele JW, Kahler DJ, Dranovsky A, Arancio O, Crary JF, Gandy S, Noggle SA (2014) Characterization and molecular profiling of PSEN1 familial Alzheimer’s disease iPSC-derived neural progenitors. PLoS ONE 9:e84547

    PubMed  PubMed Central  Google Scholar 

  • Stohr J, Watts JC, Mensinger ZL, Oehler A, Grillo SK, DeArmond SJ, Prusiner SB, Giles K (2012) Purified and synthetic Alzheimer’s amyloid beta (Abeta) prions. Proc Natl Acad Sci USA 109:11025–11030

    CAS  PubMed  PubMed Central  Google Scholar 

  • Stohr J, Condello C, Watts JC, Bloch L, Oehler A, Nick M, DeArmond SJ, Giles K, DeGrado WF, Prusiner SB (2014) Distinct synthetic Abeta prion strains producing different amyloid deposits in bigenic mice. Proc Natl Acad Sci USA 111:10329–10334

    CAS  PubMed  PubMed Central  Google Scholar 

  • Taniguchi T, Kawamata T, Mukai H, Hasegawa H, Isagawa T, Yasuda M, Hashimoto T, Terashima A, Nakai M, Mori H, Ono Y, Tanaka C (2001) Phosphorylation of tau is regulated by PKN. J Biol Chem 276:10025–10031

    CAS  PubMed  Google Scholar 

  • Thomas SM, Brugge JS (1997) Cellular functions regulated by Src family kinases. Annu Rev Cell Dev Biol 13:513–609

    CAS  PubMed  Google Scholar 

  • Tomic JL, Pensalfini A, Head E, Glabe CG (2009) Soluble fibrillar oligomer levels are elevated in Alzheimer’s disease brain and correlate with cognitive dysfunction. Neurobiol Dis 35:352–358

    CAS  PubMed  PubMed Central  Google Scholar 

  • Trotta T, Porro C, Calvello R, Panaro MA (2014) Biological role of Toll-like receptor-4 in the brain. J Neuroimmunol 268:1–12

    CAS  PubMed  Google Scholar 

  • Tschampa HJ, Neumann M, Zerr I, Henkel K, Schroter A, Schulz-Schaeffer WJ, Steinhoff BJ, Kretzschmar HA, Poser S (2001) Patients with Alzheimer’s disease and dementia with Lewy bodies mistaken for Creutzfeldt–Jakob disease. J Neurol Neurosurg Psychiatry 71:33–39

    CAS  PubMed  PubMed Central  Google Scholar 

  • Tsutsui S, Hahn JN, Johnson TA, Ali Z, Jirik FR (2008) Absence of the cellular prion protein exacerbates and prolongs neuroinflammation in experimental autoimmune encephalomyelitis. Am J Pathol 173:1029–1041

    CAS  PubMed  PubMed Central  Google Scholar 

  • Ueda K, Fukushima H, Masliah E, Xia Y, Iwai A, Yoshimoto M, Otero DA, Kondo J, Ihara Y, Saitoh T (1993) Molecular cloning of cDNA encoding an unrecognized component of amyloid in Alzheimer disease. Proc Natl Acad Sci USA 90:11282–11286

    CAS  PubMed  PubMed Central  Google Scholar 

  • Ueda K, Saitoh T, Mori H (1994) Tissue-dependent alternative splicing of mRNA for NACP, the precursor of non-A beta component of Alzheimer’s disease amyloid. Biochem Biophys Res Commun 205:1366–1372

    CAS  PubMed  Google Scholar 

  • Um JW, Nygaard HB, Heiss JK, Kostylev MA, Stagi M, Vortmeyer A, Wisniewski T, Gunther EC, Strittmatter SM (2012) Alzheimer amyloid-beta oligomer bound to postsynaptic prion protein activates Fyn to impair neurons. Nat Neurosci 15:1227–1235

    CAS  PubMed  PubMed Central  Google Scholar 

  • Um JW, Kaufman AC, Kostylev M, Heiss JK, Stagi M, Takahashi H, Kerrisk ME, Vortmeyer A, Wisniewski T, Koleske AJ, Gunther EC, Nygaard HB, Strittmatter SM (2013) Metabotropic glutamate receptor 5 is a coreceptor for Alzheimer abeta oligomer bound to cellular prion protein. Neuron 79:887–902

    CAS  PubMed  PubMed Central  Google Scholar 

  • Van Everbroeck B, Dobbeleir I, De Waele M, De Deyn P, Martin JJ, Cras P (2004) Differential diagnosis of 201 possible Creutzfeldt–Jakob disease patients. J Neurol 251:298–304

    PubMed  Google Scholar 

  • Vassar R (2004) BACE1: the beta-secretase enzyme in Alzheimer’s disease. J Mol Neurosci 23:105–114

    CAS  PubMed  Google Scholar 

  • Veerhuis R, Van Breemen MJ, Hoozemans JM, Morbin M, Ouladhadj J, Tagliavini F, Eikelenboom P (2003) Amyloid beta plaque-associated proteins C1q and SAP enhance the Abeta1-42 peptide-induced cytokine secretion by adult human microglia in vitro. Acta Neuropathol 105:135–144

    CAS  PubMed  Google Scholar 

  • Vos T, Allen C, Arora M, Barber RM, Bhutta ZA, Brown A, Carter A, Casey DC, Charlson FJ, Chen AZ et al (2016) Global, regional, and national incidence, prevalence, and years lived with disability for 310 diseases and injuries, 1990–2015: a systematic analysis for the Global Burden of Disease Study 2015. Lancet 388:1545–1602

    Google Scholar 

  • Wang HZ, Bi R, Hu QX, Xiang Q, Zhang C, Zhang DF, Zhang W, Ma X, Guo W, Deng W, Zhao L, Ni P, Li M, Fang Y, Li T, Yao YG (2016) Validating GWAS-identified risk loci for Alzheimer’s disease in Han Chinese populations. Mol Neurobiol 53:379–390

    CAS  PubMed  Google Scholar 

  • Watson CP (1979) Clinical similarity of Alzheimer and Creutzfeldt–Jakob disease. Ann Neurol 6:368–369

    CAS  PubMed  Google Scholar 

  • Watts JC, Prusiner SB (2018) beta-amyloid prions and the pathobiology of Alzheimer’s disease. Cold Spring Harb Perspect Med 8:023507

    Google Scholar 

  • Watts JC, Condello C, Stohr J, Oehler A, Lee J, DeArmond SJ, Lannfelt L, Ingelsson M, Giles K, Prusiner SB (2014) Serial propagation of distinct strains of Abeta prions from Alzheimer’s disease patients. Proc Natl Acad Sci USA 111:10323–10328

    CAS  PubMed  PubMed Central  Google Scholar 

  • Weingarten MD, Lockwood AH, Hwo SY, Kirschner MW (1975) A protein factor essential for microtubule assembly. Proc Natl Acad Sci USA 72:1858–1862

    CAS  PubMed  PubMed Central  Google Scholar 

  • Weinreb PH, Zhen W, Poon AW, Conway KA, Lansbury PT Jr (1996) NACP, a protein implicated in Alzheimer’s disease and learning, is natively unfolded. Biochemistry 35:13709–13715

    CAS  PubMed  Google Scholar 

  • Westman G, Blomberg J, Yun Z, Lannfelt L, Ingelsson M, Eriksson BM (2017) Decreased HHV-6 IgG in Alzheimer’s disease. Front Neurol 8:40

    PubMed  PubMed Central  Google Scholar 

  • Willingham S, Outeiro TF, DeVit MJ, Lindquist SL, Muchowski PJ (2003) Yeast genes that enhance the toxicity of a mutant huntingtin fragment or alpha-synuclein. Science 302:1769–1772

    CAS  PubMed  Google Scholar 

  • Wisniewski HM, Merz GS, Carp RI (1984) Senile dementia of the Alzheimer type: possibility of infectious etiology in genetically susceptible individuals. Acta Neurol Scand Suppl 99:91–97

    CAS  PubMed  Google Scholar 

  • Wojtowicz WM, Farzan M, Joyal JL, Carter K, Babcock GJ, Israel DI, Sodroski J, Mirzabekov T (2002) Stimulation of enveloped virus infection by beta-amyloid fibrils. J Biol Chem 277:35019–35024

    CAS  PubMed  Google Scholar 

  • World Health Organization (WHO) (2003) WHO manual for surveillance of human transmissible spongiform encephalopathies, including variant Creutzfeldt–Jakob disease. World Health Organization, Geneva

    Google Scholar 

  • Wozniak MA, Shipley SJ, Combrinck M, Wilcock GK, Itzhaki RF (2005) Productive herpes simplex virus in brain of elderly normal subjects and Alzheimer’s disease patients. J Med Virol 75:300–306

    PubMed  Google Scholar 

  • Wozniak MA, Itzhaki RF, Shipley SJ, Dobson CB (2007) Herpes simplex virus infection causes cellular beta-amyloid accumulation and secretase upregulation. Neurosci Lett 429:95–100

    CAS  PubMed  Google Scholar 

  • Wu GR, Mu TC, Gao ZX, Wang J, Sy MS, Li CY (2017) Prion protein is required for tumor necrosis factor alpha (TNFalpha)-triggered nuclear factor kappaB (NF-kappaB) signaling and cytokine production. J Biol Chem 292:18747–18759

    CAS  PubMed  PubMed Central  Google Scholar 

  • Xia Y, Saitoh T, Ueda K, Tanaka S, Chen X, Hashimoto M, Hsu L, Conrad C, Sundsmo M, Yoshimoto M, Thal L, Katzman R, Masliah E (2001) Characterization of the human alpha-synuclein gene: genomic structure, transcription start site, promoter region and polymorphisms. J Alzheimers Dis 3:485–494

    PubMed  Google Scholar 

  • Yang X, Zhang Y, Zhang L, He T, Zhang J, Li C (2014) Prion protein and cancers. Acta Biochim Biophys Sin (Shanghai) 46:431–440

    CAS  Google Scholar 

  • Yi CW, Wang LQ, Huang JJ, Pan K, Chen J, Liang Y (2018) Glycosylation significantly inhibits the aggregation of human prion protein and decreases its cytotoxicity. Sci Rep 8:12603

    PubMed  PubMed Central  Google Scholar 

  • Yokota O, Terada S, Ishizu H, Ujike H, Ishihara T, Nakashima H, Yasuda M, Kitamura Y, Ueda K, Checler F, Kuroda S (2002) NACP/alpha-synuclein, NAC, and beta-amyloid pathology of familial Alzheimer’s disease with the E184D presenilin-1 mutation: a clinicopathological study of two autopsy cases. Acta Neuropathol 104:637–648

    CAS  PubMed  Google Scholar 

  • You H, Tsutsui S, Hameed S, Kannanayakal TJ, Chen L, Xia P, Engbers JD, Lipton SA, Stys PK, Zamponi GW (2012) Abeta neurotoxicity depends on interactions between copper ions, prion protein, and N-methyl-d-aspartate receptors. Proc Natl Acad Sci USA 109:1737–1742

    CAS  PubMed  PubMed Central  Google Scholar 

  • Younan ND, Sarell CJ, Davies P, Brown DR, Viles JH (2013) The cellular prion protein traps Alzheimer’s Abeta in an oligomeric form and disassembles amyloid fibers. Faseb j 27:1847–1858

    CAS  PubMed  PubMed Central  Google Scholar 

  • Younan ND, Chen KF, Rose RS, Crowther DC, Viles JH (2018) Prion protein stabilizes amyloid-beta (Abeta) oligomers and enhances Abeta neurotoxicity in a Drosophila model of Alzheimer’s disease. J Biol Chem 293:13090–13099

    CAS  PubMed  PubMed Central  Google Scholar 

  • Zatta P, Drago D, Bolognin S, Sensi SL (2009) Alzheimer’s disease, metal ions and metal homeostatic therapy. Trends Pharmacol Sci 30:346–355

    CAS  PubMed  Google Scholar 

  • Zheng L, Longfei J, Jing Y, Xinqing Z, Haiqing S, Haiyan L, Fen W, Xiumin D, Jianping J (2008) PRNP mutations in a series of apparently sporadic neurodegenerative dementias in China. Am J Med Genet B Neuropsychiatr Genet 147:938–944

    Google Scholar 

Download references

Acknowledgments

This work was supported by National Natural Science Foundation of China (31670170 and 31270209), by Ministry of Science and Technology of the People’s Republic of China (2018YFA0507201).

Author information

Authors and Affiliations

  1. School of Chemistry, Chemical Engineering and Life Sciences, Wuhan University of Technology, Wuhan, 430070, China

    Chang Kong, Hao Xie & Taolei Sun

  2. State Key Laboratory of Virology, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan, 430071, China

    Chang Kong, Zhenxing Gao, Ming Shao, Huan Li, Run Shi, Lili Cai, Shanshan Gao & Chaoyang Li

  3. Affiliated Cancer Hospital, Institute of Guangzhou Medical University, Guangzhou, 510095, China

    Chang Kong & Chaoyang Li

Authors
  1. Chang Kong
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Hao Xie
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Zhenxing Gao
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Ming Shao
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Huan Li
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Run Shi
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Lili Cai
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Shanshan Gao
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Taolei Sun
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Chaoyang Li
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Chaoyang Li.

Ethics declarations

Conflict of interest

The authors declare that they have no conflict of interest.

Animal and Human Rights Statement

This article does not contain any studies with human or animal subjects performed by any of the authors.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Kong, C., Xie, H., Gao, Z. et al. Binding between Prion Protein and Aβ Oligomers Contributes to the Pathogenesis of Alzheimer’s Disease. Virol. Sin. 34, 475–488 (2019). https://doi.org/10.1007/s12250-019-00124-1

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12250-019-00124-1

Keywords

Search

Navigation