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Membrane Biophysics and Mechanics in Alzheimer's Disease

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Abstract

Alzheimer's disease is a chronic neurodegenerative disorder characterized by neuronal loss, cerebrovascular inflammation, and accumulation of senile plaques in the brain parenchyma and cerebral blood vessels. Amyloid-β peptide (Aβ), a major component of senile plaques, has been shown to exert multiple toxic effects to neurons, astrocytes, glial cells, and brain endothelium. Oligomeric Aβ can disturb the structure and function of cell membranes and alter membrane mechanical properties, such as membrane fluidity and molecular order. Much of these effects are attributed to their capability to trigger oxidative stress and inflammation. In this review, we discuss the effects of Aβ on neuronal cells, astrocytes, and cerebral endothelial cells with special emphasis on cell membrane properties and cell functions.

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References

  1. Frautschy SA, Yang F, Irrizarry M, Hyman B, Saido TC, Hsiao K, Cole GM (1998) Microglial response to amyloid plaques in APPsw transgenic mice. Am J Pathol 152:307–317

    CAS  PubMed  Google Scholar 

  2. McGeer PL, Itagaki S, Tago H, McGeer EG (1987) Reactive microglia in patients with senile dementia of the Alzheimer type are positive for the histocompatibility glycoprotein HLA-DR. Neurosci Lett 79:195–200

    CAS  PubMed  Google Scholar 

  3. Maat-Schieman ML, van Duinen SG, Rozemuller AJ, Haan J, Roos RA (1997) Association of vascular amyloid beta and cells of the mononuclear phagocyte system in hereditary cerebral hemorrhage with amyloidosis (Dutch) and Alzheimer disease. J Neuropathol Exp Neurol 56:273–284

    CAS  PubMed  Google Scholar 

  4. Uchihara T, Akiyama H, Kondo H, Ikeda K (1997) Activated microglial cells are colocalized with perivascular deposits of amyloid-beta protein in Alzheimer's disease brain. Stroke 28:1948–1950

    CAS  PubMed  Google Scholar 

  5. Dickson DW (1999) Microglia in Alzheimer's disease and transgenic models. How close the fit? Am J Pathol 154:1627–1631

    CAS  PubMed  Google Scholar 

  6. Stalder M, Phinney A, Probst A, Sommer B, Staufenbiel M, Jucker M (1999) Association of microglia with amyloid plaques in brains of APP23 transgenic mice. Am J Pathol 154:1673–1684

    CAS  PubMed  Google Scholar 

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

    CAS  PubMed  Google Scholar 

  8. Selkoe DJ (2000) The origins of Alzheimer disease: a is for amyloid. JAMA 283:1615–1617

    CAS  PubMed  Google Scholar 

  9. Cleary JP, Walsh DM, Hofmeister JJ, Shankar GM, Kuskowski MA, Selkoe DJ, Ashe KH (2005) Natural oligomers of the amyloid-beta protein specifically disrupt cognitive function. Nat Neurosci 8:79–84

    CAS  PubMed  Google Scholar 

  10. Mucke L, Masliah E, Yu GQ, Mallory M, Rockenstein EM, Tatsuno G, Hu K, Kholodenko D, Johnson-Wood K, McConlogue L (2000) High-level neuronal expression of abeta 1–42 in wild-type human amyloid protein precursor transgenic mice: synaptotoxicity without plaque formation. J Neurosci 20:4050–4058

    CAS  PubMed  Google Scholar 

  11. Resende R, Ferreiro E, Pereira C, Resende de Oliveira C (2008) Neurotoxic effect of oligomeric and fibrillar species of amyloid-beta peptide 1–42: involvement of endoplasmic reticulum calcium release in oligomer-induced cell death. Neuroscience 155:725–737

    CAS  PubMed  Google Scholar 

  12. Walsh DM, Klyubin I, Fadeeva JV, Rowan MJ, Selkoe DJ (2002) Amyloid-beta oligomers: their production, toxicity and therapeutic inhibition. Biochem Soc Trans 30:552–557

    CAS  PubMed  Google Scholar 

  13. Westerman MA, Cooper-Blacketer D, Mariash A, Kotilinek L, Kawarabayashi T, Younkin LH, Carlson GA, Younkin SG, Ashe KH (2002) The relationship between Abeta and memory in the Tg2576 mouse model of Alzheimer's disease. J Neurosci 22:1858–1867

    CAS  PubMed  Google Scholar 

  14. Hardy JA, Higgins GA (1992) Alzheimer's disease: the amyloid cascade hypothesis. Science 256:184–185

    CAS  PubMed  Google Scholar 

  15. Hellstrom IC, Danik M, Luheshi GN, Williams S (2005) Chronic LPS exposure produces changes in intrinsic membrane properties and a sustained IL-beta-dependent increase in GABAergic inhibition in hippocampal CA1 pyramidal neurons. Hippocampus 15:656–664

    CAS  PubMed  Google Scholar 

  16. Ditaranto K, Tekirian TL, Yang AJ (2001) Lysosomal membrane damage in soluble Abeta-mediated cell death in Alzheimer's disease. Neurobiol Dis 8:19–31

    CAS  PubMed  Google Scholar 

  17. Klein J (2000) Membrane breakdown in acute and chronic neurodegeneration: focus on choline-containing phospholipids. J Neural Transm 107:1027–1063

    CAS  PubMed  Google Scholar 

  18. Yao JK, Wengenack TM, Curran GL, Poduslo JF (2009) Reduced membrane lipids in the cortex of Alzheimer's disease transgenic mice. Neurochem Res 34:102–108

    CAS  PubMed  Google Scholar 

  19. Simakova O, Arispe NJ (2007) The cell-selective neurotoxicity of the Alzheimer's Abeta peptide is determined by surface phosphatidylserine and cytosolic ATP levels. Membrane binding is required for Abeta toxicity. J Neurosci 27:13719–13729

    CAS  PubMed  Google Scholar 

  20. Esposito C, Tedeschi A, Scrima M, D'Errico G, Ottaviani MF, Rovero P, D'Ursi AM (2006) Exploring interaction of beta-amyloid segment (25-35) with membrane models through paramagnetic probes. J Pept Sci 12:766–774

    CAS  PubMed  Google Scholar 

  21. Bokvist M, Lindstrom F, Watts A, Grobner G (2004) Two types of Alzheimer's beta-amyloid (1–40) peptide membrane interactions: aggregation preventing transmembrane anchoring versus accelerated surface fibril formation. J Mol Biol 335:1039–1049

    CAS  PubMed  Google Scholar 

  22. Williamson R, Usardi A, Hanger DP, Anderton BH (2008) Membrane-bound beta-amyloid oligomers are recruited into lipid rafts by a fyn-dependent mechanism. FASEB J 22:1552–1559

    CAS  PubMed  Google Scholar 

  23. Wahlstrom A, Hugonin L, Peralvarez-Marin A, Jarvet J, Graslund A (2008) Secondary structure conversions of Alzheimer's Abeta(1–40) peptide induced by membrane-mimicking detergents. FEBS J 275:5117–5128

    PubMed  Google Scholar 

  24. Verdier Y, Zarandi M, Penke B (2004) Amyloid beta-peptide interactions with neuronal and glial cell plasma membrane: binding sites and implications for Alzheimer's disease. J Pept Sci 10:229–248

    CAS  PubMed  Google Scholar 

  25. Verdier Y, Penke B (2004) Binding sites of amyloid beta-peptide in cell plasma membrane and implications for Alzheimer's disease. Curr Protein Pept Sci 5:19–31

    CAS  PubMed  Google Scholar 

  26. Wong PT, Schauerte JA, Wisser KC, Ding H, Lee EL, Steel DG, Gafni A (2009) Amyloid-beta membrane binding and permeabilization are distinct processes influenced separately by membrane charge and fluidity. J Mol Biol 386:81–96

    CAS  PubMed  Google Scholar 

  27. Blanchard BJ, Thomas VL, Ingram VM (2002) Mechanism of membrane depolarization caused by the Alzheimer Abeta1–42 peptide. Biochem Biophys Res Commun 293:1197–1203

    CAS  PubMed  Google Scholar 

  28. Vaisid T, Kosower NS, Elkind E, Barnoy S (2008) Amyloid beta peptide toxicity in differentiated PC12 cells: calpain–calpastatin, caspase, and membrane damage. J Neurosci Res 86:2314–2325

    CAS  PubMed  Google Scholar 

  29. Murray IV, Sindoni ME, Axelsen PH (2005) Promotion of oxidative lipid membrane damage by amyloid beta proteins. Biochemistry 44:12606–12613

    CAS  PubMed  Google Scholar 

  30. Ditaranto-Desimone K, Saito M, Tekirian TL, Berg M, Dubowchik G, Soreghan B, Thomas S, Marks N, Yang AJ (2003) Neuronal endosomal/lysosomal membrane destabilization activates caspases and induces abnormal accumulation of the lipid secondary messenger ceramide. Brain Res Bull 59:523–531

    CAS  PubMed  Google Scholar 

  31. Reid PC, Urano Y, Kodama T, Hamakubo T (2007) Alzheimer's disease: cholesterol, membrane rafts, isoprenoids and statins. J Cell Mol Med 11:383–392

    CAS  PubMed  Google Scholar 

  32. Wood WG, Schroeder F, Igbavboa U, Avdulov NA, Chochina SV (2002) Brain membrane cholesterol domains, aging and amyloid beta-peptides. Neurobiol Aging 23:685–694

    CAS  PubMed  Google Scholar 

  33. Eckert GP, Kirsch C, Muller WE (2003) Brain-membrane cholesterol in Alzheimer's disease. J Nutr Health Aging 7:18–23

    CAS  PubMed  Google Scholar 

  34. Lynch C, Mobley W (2000) Comprehensive theory of Alzheimer's disease. The effects of cholesterol on membrane receptor trafficking. Ann N Y Acad Sci 924:104–111

    CAS  PubMed  Google Scholar 

  35. Chochina SV, Avdulov NA, Igbavboa U, Cleary JP, O'Hare EO, Wood WG (2001) Amyloid beta-peptide1–40 increases neuronal membrane fluidity: role of cholesterol and brain region. J Lipid Res 42:1292–1297

    CAS  PubMed  Google Scholar 

  36. Kojro E, Gimpl G, Lammich S, Marz W, Fahrenholz F (2001) Low cholesterol stimulates the nonamyloidogenic pathway by its effect on the alpha-secretase ADAM 10. Proc Natl Acad Sci U S A 98:5815–5820

    CAS  PubMed  Google Scholar 

  37. Eckert GP, Kirsch C, Leutz S, Wood WG, Muller WE (2003) Cholesterol modulates amyloid beta-peptide's membrane interactions. Pharmacopsychiatry 36(Suppl 2):S136–S143

    CAS  PubMed  Google Scholar 

  38. Ji SR, Wu Y, Sui SF (2002) Cholesterol is an important factor affecting the membrane insertion of beta-amyloid peptide (A beta 1–40), which may potentially inhibit the fibril formation. J Biol Chem 277:6273–6279

    CAS  PubMed  Google Scholar 

  39. Abad-Rodriguez J, Ledesma MD, Craessaerts K, Perga S, Medina M, Delacourte A, Dingwall C, De Strooper B, Dotti CG (2004) Neuronal membrane cholesterol loss enhances amyloid peptide generation. J Cell Biol 167:953–960

    CAS  PubMed  Google Scholar 

  40. Arispe N, Doh M (2002) Plasma membrane cholesterol controls the cytotoxicity of Alzheimer's disease AbetaP (1–40) and (1–42) peptides. FASEB J 16:1526–1536

    CAS  PubMed  Google Scholar 

  41. Sponne I, Fifre A, Koziel V, Oster T, Olivier JL, Pillot T (2004) Membrane cholesterol interferes with neuronal apoptosis induced by soluble oligomers but not fibrils of amyloid-beta peptide. FASEB J 18:836–838

    CAS  PubMed  Google Scholar 

  42. Lin MS, Chen LY, Wang SS, Chang Y, Chen WY (2008) Examining the levels of ganglioside and cholesterol in cell membrane on attenuation the cytotoxicity of beta-amyloid peptide. Colloids Surf B Biointerfaces 65:172–177

    CAS  PubMed  Google Scholar 

  43. Nicholson AM, Ferreira A (2009) Increased membrane cholesterol might render mature hippocampal neurons more susceptible to beta-amyloid-induced calpain activation and tau toxicity. J Neurosci 29:4640–4651

    CAS  PubMed  Google Scholar 

  44. Curtain CC, Ali FE, Smith DG, Bush AI, Masters CL, Barnham KJ (2003) Metal ions, pH, and cholesterol regulate the interactions of Alzheimer's disease amyloid-beta peptide with membrane lipid. J Biol Chem 278:2977–2982

    CAS  PubMed  Google Scholar 

  45. Stutzmann GE, Caccamo A, LaFerla FM, Parker I (2004) Dysregulated IP3 signaling in cortical neurons of knock-in mice expressing an Alzheimer's-linked mutation in presenilin1 results in exaggerated Ca2+ signals and altered membrane excitability. J Neurosci 24:508–513

    CAS  PubMed  Google Scholar 

  46. Barbar E, Rola-Pleszczynski M, Payet MD, Dupuis G (2003) Protein kinase C inhibits the transplasma membrane influx of Ca2+ triggered by 4-aminopyridine in Jurkat T lymphocytes. Biochim Biophys Acta 1622:89–98

    CAS  PubMed  Google Scholar 

  47. Qin Y, Qi JS, Qiao JT (2006) Apolipoprotein E4 suppresses delayed-rectifier potassium channels in membrane patches excised from hippocampal neurons. Synapse 59:82–91

    CAS  PubMed  Google Scholar 

  48. Lin H, Zhu YJ, Lal R (1999) Amyloid beta protein (1–40) forms calcium-permeable, Zn2+-sensitive channel in reconstituted lipid vesicles. Biochemistry 38:11189–11196

    CAS  PubMed  Google Scholar 

  49. Rhee SK, Quist AP, Lal R (1998) Amyloid beta protein-(1–42) forms calcium-permeable, Zn2+-sensitive channel. J Biol Chem 273:13379–13382

    CAS  PubMed  Google Scholar 

  50. Ye C, Ho-Pao CL, Kanazirska M, Quinn S, Rogers K, Seidman CE, Seidman JG, Brown EM, Vassilev PM (1997) Amyloid-beta proteins activate Ca(2+)-permeable channels through calcium-sensing receptors. J Neurosci Res 47:547–554

    CAS  PubMed  Google Scholar 

  51. Arispe N, Rojas E, Pollard HB (1993) Alzheimer disease amyloid beta protein forms calcium channels in bilayer membranes: blockade by tromethamine and aluminum. Proc Natl Acad Sci U S A 90:567–571

    CAS  PubMed  Google Scholar 

  52. Sberna G, Saez-Valero J, Beyreuther K, Masters CL, Small DH (1997) The amyloid beta-protein of Alzheimer's disease increases acetylcholinesterase expression by increasing intracellular calcium in embryonal carcinoma P19 cells. J Neurochem 69:1177–1184

    Article  CAS  PubMed  Google Scholar 

  53. Abramov AY, Canevari L, Duchen MR (2004) Calcium signals induced by amyloid beta peptide and their consequences in neurons and astrocytes in culture. Biochim Biophys Acta 1742:81–87

    CAS  PubMed  Google Scholar 

  54. Ho R, Ortiz D, Shea TB (2001) Amyloid-beta promotes calcium influx and neurodegeneration via stimulation of L voltage-sensitive calcium channels rather than NMDA channels in cultured neurons. J Alzheimers Dis 3:479–483

    CAS  PubMed  Google Scholar 

  55. Niu Y, Su Z, Zhao C, Song B, Zhang X, Zhao N, Shen X, Gong Y (2009) Effect of amyloid beta on capacitive calcium entry in neural 2a cells. Brain Res Bull 78:152–157

    CAS  PubMed  Google Scholar 

  56. Berrocal M, Marcos D, Sepulveda MR, Perez M, Avila J, Mata AM (2009) Altered Ca2+ dependence of synaptosomal plasma membrane Ca2+-ATPase in human brain affected by Alzheimer's disease. FASEB J 23:1826–1834

    CAS  PubMed  Google Scholar 

  57. Koyama Y, Matsuzaki S, Gomi F, Yamada K, Katayama T, Sato K, Kumada T, Fukuda A, Matsuda S, Tano Y, Tohyama M (2008) Induction of amyloid beta accumulation by ER calcium disruption and resultant upregulation of angiogenic factors in ARPE19 cells. Invest Ophthalmol Vis Sci 49:2376–2383

    PubMed  Google Scholar 

  58. Ferreiro E, Oliveira CR, Pereira CM (2008) The release of calcium from the endoplasmic reticulum induced by amyloid-beta and prion peptides activates the mitochondrial apoptotic pathway. Neurobiol Dis 30:331–342

    CAS  PubMed  Google Scholar 

  59. Isaacs AM, Senn DB, Yuan M, Shine JP, Yankner BA (2006) Acceleration of amyloid beta-peptide aggregation by physiological concentrations of calcium. J Biol Chem 281:27916–27923

    CAS  PubMed  Google Scholar 

  60. Stephenson D, Rash K, Smalstig B, Roberts E, Johnstone E, Sharp J, Panetta J, Little S, Kramer R, Clemens J (1999) Cytosolic phospholipase A2 is induced in reactive glia following different forms of neurodegeneration. Glia 27:110–128

    CAS  PubMed  Google Scholar 

  61. Stephenson DT, Lemere CA, Selkoe DJ, Clemens JA (1996) Cytosolic phospholipase A2 (cPLA2) immunoreactivity is elevated in Alzheimer's disease brain. Neurobiol Dis 3:51–63

    CAS  PubMed  Google Scholar 

  62. Moses GS, Jensen MD, Lue LF, Walker DG, Sun AY, Simonyi A, Sun GY (2006) Secretory PLA2-IIA: a new inflammatory factor for Alzheimer's disease. J Neuroinflammation 3:28

    PubMed  Google Scholar 

  63. Sun GY, Xu J, Jensen MD, Simonyi A (2004) Phospholipase A2 in the central nervous system: implications for neurodegenerative diseases. J Lipid Res 45:205–213

    CAS  PubMed  Google Scholar 

  64. Murakami M, Kudo I (2002) Phospholipase A2. J Biochem 131:285–292

    CAS  PubMed  Google Scholar 

  65. Muralikrishna Adibhatla R, Hatcher JF (2006) Phospholipase A2, reactive oxygen species, and lipid peroxidation in cerebral ischemia. Free Radic Biol Med 40:376–387

    CAS  PubMed  Google Scholar 

  66. Sun GY, Horrocks LA, Farooqui AA (2007) The roles of NADPH oxidase and phospholipases A2 in oxidative and inflammatory responses in neurodegenerative diseases. J Neurochem 103:1–16

    CAS  PubMed  Google Scholar 

  67. Farooqui AA, Ong WY, Horrocks LA (2006) Inhibitors of brain phospholipase A2 activity: their neuropharmacological effects and therapeutic importance for the treatment of neurologic disorders. Pharmacol Rev 58:591–620

    CAS  PubMed  Google Scholar 

  68. Farooqui AA, Horrocks LA (2006) Phospholipase A2-generated lipid mediators in the brain: the good, the bad, and the ugly. Neuroscientist 12:245–260

    CAS  PubMed  Google Scholar 

  69. Yagami T (2006) Cerebral arachidonate cascade in dementia: Alzheimer's disease and vascular dementia. Curr Neuropharmacol 4:87–100

    CAS  PubMed  Google Scholar 

  70. Yedgar S, Cohen Y, Shoseyov D (2006) Control of phospholipase A2 activities for the treatment of inflammatory conditions. Biochim Biophys Acta 1761:1373–1382

    CAS  PubMed  Google Scholar 

  71. Dennis EA (1994) Diversity of group types, regulation, and function of phospholipase A2. J Biol Chem 269:13057–13060

    CAS  PubMed  Google Scholar 

  72. Sun GY, Xu J, Jensen MD, Yu S, Wood WG, Gonzalez FA, Simonyi A, Sun AY, Weisman GA (2005) Phospholipase A2 in astrocytes: responses to oxidative stress, inflammation, and G protein-coupled receptor agonists. Mol Neurobiol 31:27–41

    CAS  PubMed  Google Scholar 

  73. Colangelo V, Schurr J, Ball MJ, Pelaez RP, Bazan NG, Lukiw WJ (2002) Gene expression profiling of 12633 genes in Alzheimer hippocampal CA1: transcription and neurotrophic factor down-regulation and up-regulation of apoptotic and pro-inflammatory signaling. J Neurosci Res 70:462–473

    CAS  PubMed  Google Scholar 

  74. Bate C, Williams A (2007) Squalestatin protects neurons and reduces the activation of cytoplasmic phospholipase A2 by Abeta(1–42). Neuropharmacology 53:222–231

    CAS  PubMed  Google Scholar 

  75. Kriem B, Sponne I, Fifre A, Malaplate-Armand C, Lozac'h-Pillot K, Koziel V, Yen-Potin FT, Bihain B, Oster T, Olivier JL, Pillot T (2005) Cytosolic phospholipase A2 mediates neuronal apoptosis induced by soluble oligomers of the amyloid-beta peptide. FASEB J 19:85–87

    CAS  PubMed  Google Scholar 

  76. Chalimoniuk M, Stolecka A, Cakala M, Hauptmann S, Schulz K, Lipka U, Leuner K, Eckert A, Muller WE, Strosznajder JB (2007) Amyloid beta enhances cytosolic phospholipase A2 level and arachidonic acid release via nitric oxide in APP-transfected PC12 cells. Acta Biochim Pol 54:611–623

    CAS  PubMed  Google Scholar 

  77. Shelat PB, Chalimoniuk M, Wang JH, Strosznajder JB, Lee JC, Sun AY, Simonyi A, Sun GY (2008) Amyloid beta peptide and NMDA induce ROS from NADPH oxidase and AA release from cytosolic phospholipase A2 in cortical neurons. J Neurochem 106:45–55

    CAS  PubMed  Google Scholar 

  78. Hicks JB, Lai Y, Sheng W, Yang X, Zhu D, Sun GY, Lee JC (2008) Amyloid-beta peptide induces temporal membrane biphasic changes in astrocytes through cytosolic phospholipase A2. Biochim Biophys Acta 1778:2512–2519

    CAS  PubMed  Google Scholar 

  79. Lingwood D, Simons K. Lipid rafts as a membrane-organizing principle. Science 327:46-50

  80. Lingwood D, Kaiser HJ, Levental I, Simons K (2009) Lipid rafts as functional heterogeneity in cell membranes. Biochem Soc Trans 37:955–960

    CAS  PubMed  Google Scholar 

  81. Parasassi T, De Stasio G, d'Ubaldo A, Gratton E (1990) Phase fluctuation in phospholipid membranes revealed by Laurdan fluorescence. Biophys J 57:1179–1186

    CAS  PubMed  Google Scholar 

  82. Parasassi T, De Stasio G, Ravagnan G, Rusch RM, Gratton E (1991) Quantitation of lipid phases in phospholipid vesicles by the generalized polarization of Laurdan fluorescence. Biophys J 60:179–189

    CAS  PubMed  Google Scholar 

  83. Parasassi T, Di Stefano M, Loiero M, Ravagnan G, Gratton E (1994) Influence of cholesterol on phospholipid bilayers phase domains as detected by Laurdan fluorescence. Biophys J 66:120–132

    CAS  PubMed  Google Scholar 

  84. Parasassi T, Di Stefano M, Ravagnan G, Sapora O, Gratton E (1992) Membrane aging during cell growth ascertained by Laurdan generalized polarization. Exp Cell Res 202:432–439

    CAS  PubMed  Google Scholar 

  85. Parasassi T, Ravagnan G, Rusch RM, Gratton E (1993) Modulation and dynamics of phase properties in phospholipid mixtures detected by Laurdan fluorescence. Photochem Photobiol 57:403–410

    CAS  PubMed  Google Scholar 

  86. Waschuk SA, Elton EA, Darabie AA, Fraser PE, McLaurin JA (2001) Cellular membrane composition defines A beta-lipid interactions. J Biol Chem 276:33561–33568

    CAS  PubMed  Google Scholar 

  87. Zhu D, Hu C, Sheng W, Tan KS, Haidekker MA, Sun AY, Sun GY, Lee JC (2009) NAD(P)H oxidase-mediated reactive oxygen species production alters astrocyte membrane molecular order via phospholipase A2. Biochem J 421:201–210

    CAS  PubMed  Google Scholar 

  88. Eckert GP, Cairns NJ, Maras A, Gattaz WF, Muller WE (2000) Cholesterol modulates the membrane-disordering effects of beta-amyloid peptides in the hippocampus: specific changes in Alzheimer's disease. Dement Geriatr Cogn Disord 11:181–186

    CAS  PubMed  Google Scholar 

  89. Gattaz WF, Maras A, Cairns NJ, Levy R, Forstl H (1995) Decreased phospholipase A2 activity in Alzheimer brains. Biol Psychiatry 37:13–17

    CAS  PubMed  Google Scholar 

  90. Ross BM, Moszczynska A, Erlich J, Kish SJ (1998) Phospholipid-metabolizing enzymes in Alzheimer's disease: increased lysophospholipid acyltransferase activity and decreased phospholipase A2 activity. J Neurochem 70:786–793

    Article  CAS  PubMed  Google Scholar 

  91. Forlenza OV, Schaeffer EL, Gattaz WF (2007) The role of phospholipase A2 in neuronal homeostasis and memory formation: implications for the pathogenesis of Alzheimer's disease. J Neural Transm 114:231–238

    CAS  PubMed  Google Scholar 

  92. Schaeffer EL, Bassi F Jr, Gattaz WF (2005) Inhibition of phospholipase A2 activity reduces membrane fluidity in rat hippocampus. J Neural Transm 112:641–647

    CAS  PubMed  Google Scholar 

  93. Reddy PH, Beal MF (2008) Amyloid beta, mitochondrial dysfunction and synaptic damage: implications for cognitive decline in aging and Alzheimer's disease. Trends Mol Med 14:45–53

    CAS  PubMed  Google Scholar 

  94. Manczak M, Park BS, Jung Y, Reddy PH (2004) Differential expression of oxidative phosphorylation genes in patients with Alzheimer's disease: implications for early mitochondrial dysfunction and oxidative damage. Neuromolecular Med 5:147–162

    CAS  PubMed  Google Scholar 

  95. Reddy PH, McWeeney S, Park BS, Manczak M, Gutala RV, Partovi D, Jung Y, Yau V, Searles R, Mori M, Quinn J (2004) Gene expression profiles of transcripts in amyloid precursor protein transgenic mice: up-regulation of mitochondrial metabolism and apoptotic genes is an early cellular change in Alzheimer's disease. Hum Mol Genet 13:1225–1240

    CAS  PubMed  Google Scholar 

  96. Devi L, Prabhu BM, Galati DF, Avadhani NG, Anandatheerthavarada HK (2006) Accumulation of amyloid precursor protein in the mitochondrial import channels of human Alzheimer's disease brain is associated with mitochondrial dysfunction. J Neurosci 26:9057–9068

    CAS  PubMed  Google Scholar 

  97. Sultana R, Perluigi M, Butterfield DA (2006) Protein oxidation and lipid peroxidation in brain of subjects with Alzheimer's disease: insights into mechanism of neurodegeneration from redox proteomics. Antioxid Redox Signal 8:2021–2037

    CAS  PubMed  Google Scholar 

  98. Wang J, Xiong S, Xie C, Markesbery WR, Lovell MA (2005) Increased oxidative damage in nuclear and mitochondrial DNA in Alzheimer's disease. J Neurochem 93:953–962

    CAS  PubMed  Google Scholar 

  99. Zhu X, Smith MA, Perry G, Aliev G (2004) Mitochondrial failures in Alzheimer's disease. Am J Alzheimers Dis Other Demen 19:345–352

    PubMed  Google Scholar 

  100. Caspersen C, Wang N, Yao J, Sosunov A, Chen X, Lustbader JW, Xu HW, Stern D, McKhann G, Yan SD (2005) Mitochondrial Abeta: a potential focal point for neuronal metabolic dysfunction in Alzheimer's disease. FASEB J 19:2040–2041

    CAS  PubMed  Google Scholar 

  101. Du H, Guo L, Fang F, Chen D, Sosunov AA, McKhann GM, Yan Y, Wang C, Zhang H, Molkentin JD, Gunn-Moore FJ, Vonsattel JP, Arancio O, Chen JX, Yan SD (2008) Cyclophilin D deficiency attenuates mitochondrial and neuronal perturbation and ameliorates learning and memory in Alzheimer's disease. Nat Med 14:1097–1105

    CAS  PubMed  Google Scholar 

  102. Hansson Petersen CA, Alikhani N, Behbahani H, Wiehager B, Pavlov PF, Alafuzoff I, Leinonen V, Ito A, Winblad B, Glaser E, Ankarcrona M (2008) The amyloid beta-peptide is imported into mitochondria via the TOM import machinery and localized to mitochondrial cristae. Proc Natl Acad Sci U S A 105:13145–13150

    CAS  PubMed  Google Scholar 

  103. Manczak M, Anekonda TS, Henson E, Park BS, Quinn J, Reddy PH (2006) Mitochondria are a direct site of A beta accumulation in Alzheimer's disease neurons: implications for free radical generation and oxidative damage in disease progression. Hum Mol Genet 15:1437–1449

    CAS  PubMed  Google Scholar 

  104. Wang X, Su B, Siedlak SL, Moreira PI, Fujioka H, Wang Y, Casadesus G, Zhu X (2008) Amyloid-beta overproduction causes abnormal mitochondrial dynamics via differential modulation of mitochondrial fission/fusion proteins. Proc Natl Acad Sci U S A 105:19318–19323

    CAS  PubMed  Google Scholar 

  105. Zhu D, Lai Y, Shelat PB, Hu C, Sun GY, Lee JC (2006) Phospholipases A2 mediate amyloid-beta peptide-induced mitochondrial dysfunction. J Neurosci 26:11111–11119

    CAS  PubMed  Google Scholar 

  106. Di Paola M, Lorusso M (2006) Interaction of free fatty acids with mitochondria: coupling, uncoupling and permeability transition. Biochim Biophys Acta 1757:1330–1337

    PubMed  Google Scholar 

  107. Hirabara SM, Silveira LR, Alberici LC, Leandro CV, Lambertucci RH, Polimeno GC, Cury Boaventura MF, Procopio J, Vercesi AE, Curi R (2006) Acute effect of fatty acids on metabolism and mitochondrial coupling in skeletal muscle. Biochim Biophys Acta 1757:57–66

    CAS  PubMed  Google Scholar 

  108. Penzo D, Petronilli V, Angelin A, Cusan C, Colonna R, Scorrano L, Pagano F, Prato M, Di Lisa F, Bernardi P (2004) Arachidonic acid released by phospholipase A(2) activation triggers Ca(2+)-dependent apoptosis through the mitochondrial pathway. J Biol Chem 279:25219–25225

    CAS  PubMed  Google Scholar 

  109. Thornton E, Vink R, Blumbergs PC, Van Den Heuvel C (2006) Soluble amyloid precursor protein alpha reduces neuronal injury and improves functional outcome following diffuse traumatic brain injury in rats. Brain Res 1094:38–46

    CAS  PubMed  Google Scholar 

  110. Haass C, Hung AY, Schlossmacher MG, Teplow DB, Selkoe DJ (1993) Beta-Amyloid peptide and a 3-kDa fragment are derived by distinct cellular mechanisms. J Biol Chem 268:3021–3024

    CAS  PubMed  Google Scholar 

  111. Koo EH, Squazzo SL (1994) Evidence that production and release of amyloid beta-protein involves the endocytic pathway. J Biol Chem 269:17386–17389

    CAS  PubMed  Google Scholar 

  112. Cordy JM, Hussain I, Dingwall C, Hooper NM, Turner AJ (2003) Exclusively targeting beta-secretase to lipid rafts by GPI-anchor addition up-regulates beta-site processing of the amyloid precursor protein. Proc Natl Acad Sci U S A 100:11735–11740

    CAS  PubMed  Google Scholar 

  113. Ehehalt R, Keller P, Haass C, Thiele C, Simons K (2003) Amyloidogenic processing of the Alzheimer beta-amyloid precursor protein depends on lipid rafts. J Cell Biol 160:113–123

    CAS  PubMed  Google Scholar 

  114. Kaether C, Haass C (2004) A lipid boundary separates APP and secretases and limits amyloid beta-peptide generation. J Cell Biol 167:809–812

    CAS  PubMed  Google Scholar 

  115. Marlow L, Cain M, Pappolla MA, Sambamurti K (2003) Beta-secretase processing of the Alzheimer's amyloid protein precursor (APP). J Mol Neurosci 20:233–239

    CAS  PubMed  Google Scholar 

  116. Tun H, Marlow L, Pinnix I, Kinsey R, Sambamurti K (2002) Lipid rafts play an important role in A beta biogenesis by regulating the beta-secretase pathway. J Mol Neurosci 19:31–35

    CAS  PubMed  Google Scholar 

  117. Vetrivel KS, Cheng H, Lin W, Sakurai T, Li T, Nukina N, Wong PC, Xu H, Thinakaran G (2004) Association of gamma-secretase with lipid rafts in post-Golgi and endosome membranes. J Biol Chem 279:44945–44954

    CAS  PubMed  Google Scholar 

  118. Sawamura N, Ko M, Yu W, Zou K, Hanada K, Suzuki T, Gong JS, Yanagisawa K, Michikawa M (2004) Modulation of amyloid precursor protein cleavage by cellular sphingolipids. J Biol Chem 279:11984–11991

    CAS  PubMed  Google Scholar 

  119. Simons M, Keller P, De Strooper B, Beyreuther K, Dotti CG, Simons K (1998) Cholesterol depletion inhibits the generation of beta-amyloid in hippocampal neurons. Proc Natl Acad Sci U S A 95:6460–6464

    CAS  PubMed  Google Scholar 

  120. von Arnim CA, von Einem B, Weber P, Wagner M, Schwanzar D, Spoelgen R, Strauss WL, Schneckenburger H (2008) Impact of cholesterol level upon APP and BACE proximity and APP cleavage. Biochem Biophys Res Commun 370:207–212

    Google Scholar 

  121. Cho HW, Kim JH, Choi S, Kim HJ (2006) Phospholipase A2 is involved in muscarinic receptor-mediated sAPPalpha release independently of cyclooxygenase or lypoxygenase activity in SH-SY5Y cells. Neurosci Lett 397:214–218

    CAS  PubMed  Google Scholar 

  122. Yang X, Sheng W, He Y, Cui J, Haidekker MA, Sun GY, Lee JC (2009) Secretory phospholipase A2 Type III enhances {alpha}-secretase-dependent amyloid precursor protein processing through alterations in membrane fluidity. J Lipid Res

  123. Fukaya T, Gondaira T, Kashiyae Y, Kotani S, Ishikura Y, Fujikawa S, Kiso Y, Sakakibara M (2007) Arachidonic acid preserves hippocampal neuron membrane fluidity in senescent rats. Neurobiol Aging 28:1179–1186

    CAS  PubMed  Google Scholar 

  124. Kogel D, Copanaki E, Hartig U, Bottner S, Peters I, Muller WE, Eckert G (2008) Modulation of membrane fluidity by omega 3 fatty acids: enhanced generation of sAPPalpha is required for the neuroprotective effects of DHA. The 38th annual meeting of the Society for Neuroscience. Washington, DC., Nov 15–19, 2008

  125. Peters I, Igbavboa U, Schutt T, Haidari S, Hartig U, Rosello X, Bottner S, Copanaki E, Deller T, Kogel D, Wood WG, Muller WE, Eckert GP (2009) The interaction of beta-amyloid protein with cellular membranes stimulates its own production. Biochim Biophys Acta 1788:964–972

    CAS  PubMed  Google Scholar 

  126. Cirrito JR, Kang JE, Lee J, Stewart FR, Verges DK, Silverio LM, Bu G, Mennerick S, Holtzman DM (2008) Endocytosis is required for synaptic activity-dependent release of amyloid-beta in vivo. Neuron 58:42–51

    CAS  PubMed  Google Scholar 

  127. Kinoshita A, Fukumoto H, Shah T, Whelan CM, Irizarry MC, Hyman BT (2003) Demonstration by FRET of BACE interaction with the amyloid precursor protein at the cell surface and in early endosomes. J Cell Sci 116:3339–3346

    CAS  PubMed  Google Scholar 

  128. Rajendran L, Schneider A, Schlechtingen G, Weidlich S, Ries J, Braxmeier T, Schwille P, Schulz JB, Schroeder C, Simons M, Jennings G, Knolker H-J, Simons K (2008) Efficient Inhibition of the Alzheimer's Disease {beta}-Secretase by Membrane Targeting. Science 320:520–523

    CAS  PubMed  Google Scholar 

  129. Schobel S, Neumann S, Hertweck M, Dislich B, Kuhn PH, Kremmer E, Seed B, Baumeister R, Haass C, Lichtenthaler SF (2008) A novel sorting nexin modulates endocytic trafficking and alpha-secretase cleavage of the amyloid precursor protein. J Biol Chem 283:14257–14268

    PubMed  Google Scholar 

  130. Small SA, Gandy S (2006) Sorting through the cell biology of Alzheimer's disease: intracellular pathways to pathogenesis. Neuron 52:15–31

    CAS  PubMed  Google Scholar 

  131. Luc B, Patrick R HOF, Andre D (1997) Brain microvascular changes in Alzheimer's disease and other dementias. Ann N Y Acad Sci 826:7–24

    Google Scholar 

  132. Berzin TM, Zipser BD, Rafii MS, Kuo--Leblanc V, Yancopoulos GD, Glass DJ, Fallon JR, Stopa EG (2000) Agrin and microvascular damage in Alzheimer's disease. Neurobiol Aging 21:349–355

    Google Scholar 

  133. Bailey TL, Rivara CB, Rocher AB, Hof PR (2004) The nature and effects of cortical microvascular pathology in aging and Alzheimer's disease. Neurol Res 26:573–578

    PubMed  Google Scholar 

  134. Kalaria RN, Pax AB (1995) Increased collagen content of cerebral microvessels in Alzheimer's disease. Brain Res 705:349–352

    CAS  PubMed  Google Scholar 

  135. Ervin JF, Pannell C, Szymanski M, Welsh-Bohmer K, Schmechel DE, Hulette CM (2004) Vascular Smooth muscle actin is reduced in Alzheimer disease brain: a quantitative analysis. J Neuropathol Exp Neurol 63:735–741

    CAS  PubMed  Google Scholar 

  136. Kalaria RN, P H (1995) Differential degeneration of the cerebral microvasculature in Alzheimer’s disease. Neuroreport 6:477–480

  137. Claudio L (1996) Ultrastructural features of the blood-brain barrier in biopsy tissue from Alzheimer's disease patients. Acta Neuropathol 91:6–14

    CAS  PubMed  Google Scholar 

  138. Aliev G, Seyidova D, Lamb BT, Obrenovich ME, Siedlak SL, Vinters HV, Friedland RP, Lamanna JC, Smith MA, Perry G (2003) Mitochondria and vascular lesions as a central target for the development of Alzheimer's disease and Alzheimer disease-like pathology in transgenic mice. Neurol Res 25:665–674

    PubMed  Google Scholar 

  139. De la Torre JC (2004) Is Alzheimer's disease a neurodegenerative or a vascular disorder? Data, dogma, and dialectics. The Lancet Neurology 3:184–190

    Google Scholar 

  140. Price JM, Chi X, Hellermann G, Sutton ET (2001) Physiological levels of beta-amyloid induce cerebral vessel dysfunction and reduce endothelial nitric oxide production. Neurol Res 23:506–512

    CAS  PubMed  Google Scholar 

  141. Emmanuelle MB, Michal T, Robert JM, Bernhard H (1997) Amyloid β-peptide induces cell monolayer albumin permeability, impairs glucose transport, and induces apoptosis in vascular endothelial cells. J Neurochem 68:1870–1881

    Google Scholar 

  142. Bhatia R, Lin HAI, Lal R (2000) Fresh and globular amyloid beta-protein (1–42) induces rapid cellular degeneration: evidence for A{beta}P channel-mediated cellular toxicity. FASEB J 14:1233–1243

    CAS  PubMed  Google Scholar 

  143. Xu J, Chen S, Ku G, Ahmed SH, Xu J, Chen H, Hsu CY (2001) Amyloid beta-peptide-induced cerebral endothelial cell death involves mitochondrial dysfunction and caspase activation. J Cereb Blood Flow Metab 21:702–710

    CAS  PubMed  Google Scholar 

  144. Park LAJ, Forster C, Kazama K, Carlson GA, Iadecola C (2004) Abeta-induced vascular oxidative stress and attenuation of functional hyperemia in mouse somatosensory cortex. Journal of Cerebral Blood Flow Metabolism 24:334–342

    CAS  PubMed  Google Scholar 

  145. Iadecola CZF, Niwa K, Eckman C, Turner SK, Fischer E, Younkin S, Borchelt DR, Hsiao KK, Carlson GA (1999) SOD1 rescues cerebral endothelial dysfunction in mice overexpressing amyloid precursor protein. Nat Neurosci 2:157–161

    CAS  PubMed  Google Scholar 

  146. Tong X-K, Nicolakakis N, Kocharyan A, Hamel E (2005) Vascular remodeling versus amyloid-beta-induced oxidative stress in the cerebrovascular dysfunctions associated with Alzheimer's disease. J Neurosci 25:11165–11174

    CAS  PubMed  Google Scholar 

  147. Yin KJ, Lee JM, Chen SD, Xu J, Hsu CY (2002) Amyloid-beta induces Smac release via AP-1/Bim activation in cerebral endothelial cells. J Neurosci 22:9764–9770

    CAS  PubMed  Google Scholar 

  148. Hsu M-J, Hsu CY, Chen B-C, Chen M-C, Ou G, Lin C-H (2007) Apoptosis signal-regulating kinase 1 in amyloid-beta-peptide-induced cerebral endothelial cell apoptosis. J Neurosci 27:5719–5729

    CAS  PubMed  Google Scholar 

  149. Grammas P, Ovase R (2001) Inflammatory factors are elevated in brain microvessels in Alzheimer's disease. Neurobiol Aging 22:837–842

    CAS  PubMed  Google Scholar 

  150. Vukic V, Callaghan D, Walker D, Lue L-F, Liu QY, Couraud P-O, Romero IA, Weksler B, Stanimirovic DB, Zhang W (2009) Expression of inflammatory genes induced by beta-amyloid peptides in human brain endothelial cells and in Alzheimer's brain is mediated by the JNK-AP1 signaling pathway. Neurobiol Dis 34:95–106

    CAS  PubMed  Google Scholar 

  151. Callaghan D, Bai J, Huang A, Vukic V, Xiong H, Jones A, Walker D, Leu LF, Beach TG, Sue L, Zhang W (2008) P4-182: inhibition of ABCG2 transport function by amyloid-beta peptide augments cellular oxidative stress and inflammatory gene expression in cells. Alzheimer's and Dementia 4:T724–T724

    Google Scholar 

  152. Park L, Anrather J, Zhou P, Frys K, Pitstick R, Younkin S, Carlson GA, Iadecola C (2005) NADPH oxidase-derived reactive oxygen species mediate the cerebrovascular dysfunction induced by the amyloid-beta-peptide. J Neurosci 25:1769–1777

    CAS  PubMed  Google Scholar 

  153. Park L, Zhou P, Pitstick R, Capone C, Anrather J, Norris EH, Younkin L, Younkin S, Carlson G, McEwen BS, Iadecola C (2008) Nox2-derived radicals contribute to neurovascular and behavioral dysfunction in mice overexpressing the amyloid precursor protein. Proc Natl Acad Sci 105:1347–1352

    CAS  PubMed  Google Scholar 

  154. Girouard H, Iadecola C (2006) Neurovascular coupling in the normal brain and in hypertension, stroke, and Alzheimer disease. J Appl Physiol 100:328–335

    CAS  PubMed  Google Scholar 

  155. Maat-Schieman ML vDS, Rozemuller AJ, Haan J, Roos RA (1997) Association of vascular amyloid beta and cells of the mononuclear phagocyte system in hereditary cerebral hemorrhage with amyloidosis (Dutch) and Alzheimer disease. J Neuropathol Exp Neurol 56:273–284

  156. Uchihara TAH, Kondo H, Ikeda K (1997) Activated microglial cells are colocalized with perivascular deposits of amyloid-beta protein in Alzheimer's disease brain. Stroke 28:1948–1950

    CAS  PubMed  Google Scholar 

  157. Selkoe DJ, Schenk D (2003) Alzheimer's disease: molecular understanding predicts amyloid-based therapeutics. Annu Rev Pharmacol Toxicol 43:545–584

    CAS  PubMed  Google Scholar 

  158. Mezey E, Chandross KJ, Harta G, Maki RA, McKercher SR (2000) Turning blood into brain: cells bearing neuronal antigens generated in vivo from bone marrow. Science 290:1779–1782

    CAS  PubMed  Google Scholar 

  159. Giri R, Selvaraj S, Miller CA, Hofman F, Yan SD, Stern D, Zlokovic BV, Kalra VK (2002) Effect of endothelial cell polarity on beta-amyloid-induced migration of monocytes across normal and AD endothelium. Am J Physiol Cell Physiol 283:C895–C904

    CAS  PubMed  Google Scholar 

  160. Francisco J. G-V, Melissa A. Moss (2008) Soluble aggregates of the amyloid-β protein activate endothelial monolayers for adhesion and subsequent transmigration of monocyte cells. J Neurochem 104:500–513

  161. Giri R, Shen Y, Stins M, Du Yan S, Schmidt AM, Stern D, Kim KS, Zlokovic B, Kalra VK (2000) Beta-amyloid-induced migration of monocytes across human brain endothelial cells involves RAGE and PECAM-1. Am J Physiol Cell Physiol 279:C1772–C1781

    CAS  PubMed  Google Scholar 

  162. Reyes Barcelo A, Gonzalez-Velasquez F, Moss M (2009) Soluble aggregates of the amyloid-beta peptide are trapped by serum albumin to enhance amyloid-beta activation of endothelial cells. Journal of Biological Engineering 3:5

    PubMed  Google Scholar 

  163. Frijns CJ, Kappelle LJ (2002) Inflammatory cell adhesion molecules in ischemic cerebrovascular disease. Stroke 33:2115–2122

    CAS  PubMed  Google Scholar 

  164. Alon R, Chen S, Puri KD, Finger EB, Springer TA (1997) The kinetics of l-selectin tethers and the mechanics of selectin-mediated rolling. J Cell Biol 138:1169–1180

    CAS  PubMed  Google Scholar 

  165. Alon R, Hammer DA, Springer TA (1995) Lifetime of the P-selectin–carbohydrate bond and its response to tensile force in hydrodynamic flow. Nature 374:539–542

    CAS  PubMed  Google Scholar 

  166. Dembo M, Torney DC, Saxman K, Hammer D (1988) The reaction-limited kinetics of membrane-to-surface adhesion and detachment. Proc R Soc Lond B Biol Sci 234:55–83

    CAS  PubMed  Google Scholar 

  167. Trache A, Trzeciakowski JP, Gardiner L, Sun Z, Muthuchamy M, Guo M, Yuan SY, Meininger GA (2005) Histamine effects on endothelial cell fibronectin interaction studied by atomic force microscopy. Biophys J 89:2888–2898

    CAS  PubMed  Google Scholar 

  168. Sun M, Northup N, Marga F, Huber T, Byfield FJ, Levitan I, Forgacs G (2007) The effect of cellular cholesterol on membrane–cytoskeleton adhesion. J Cell Sci 120:2223–2231

    CAS  PubMed  Google Scholar 

  169. Sun M, Graham JS, Hegedьs B, Marga F, Zhang Y, Forgacs G, Grandbois M (2005) Multiple membrane tethers probed by atomic force microscopy. Biophys J 89:4320–4329

    CAS  PubMed  Google Scholar 

  170. Girdhar G, Shao J-Y (2004) Membrane tether extraction from human umbilical vein endothelial cells and its implication in leukocyte rolling. Biophys J 87:3561–3568

    CAS  PubMed  Google Scholar 

  171. Girdhar G, Chen Y, Shao J-Y (2007) Double-tether extraction from human umbilical vein and dermal microvascular endothelial cells. Biophys J 92:1035–1045

    CAS  PubMed  Google Scholar 

  172. Marco S, Skaper SD (2006) Amyloid [beta]-peptide1–42 alters tight junction protein distribution and expression in brain microvessel endothelial cells. Neurosci Lett 401:219–224

    CAS  PubMed  Google Scholar 

  173. Mendoza-Naranjo A, Gonzalez-Billault C, Maccioni RB (2007) Abeta1–42 stimulates actin polymerization in hippocampal neurons through Rac1 and Cdc42 Rho GTPases. J Cell Sci 120:279–288

    CAS  PubMed  Google Scholar 

  174. Cheng S, George P, Dechun W, Ya Fang L (2002) Beta-Amyloid peptide induces formation of actin stress fibers through p38 mitogen-activated protein kinase. J Neurochem 83:828–836

    Google Scholar 

  175. Bell R, Zlokovic B (2009) Neurovascular mechanisms and blood–brain barrier disorder in Alzheimer’s disease. Acta Neuropathol 118:103–113

    CAS  PubMed  Google Scholar 

  176. Zlokovic BV (2008) New therapeutic targets in the neurovascular pathway in Alzheimer's disease. Neurotherapeutics 5:409–414

    CAS  PubMed  Google Scholar 

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Acknowledgements

This work was supported by National Institutes of Health Grants 1P01AG18357, 1R21NS052385, and 1R21AG032579.

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  1. Department of Biological Engineering, University of Missouri, 240 Agricultural Engineering Building, Columbia, MO, 65211, USA

    Xiaoguang Yang, Sholpan Askarova & James C-M. Lee

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  1. Xiaoguang Yang
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Correspondence to James C-M. Lee.

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Xiaoguang Yang and Sholpan Askarova contributed equally to the work.

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Yang, X., Askarova, S. & Lee, J.CM. Membrane Biophysics and Mechanics in Alzheimer's Disease. Mol Neurobiol 41, 138–148 (2010). https://doi.org/10.1007/s12035-010-8121-9

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