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Adult-Onset Deficiency of Mitochondrial Complex III in a Mouse Model of Alzheimer’s Disease Decreases Amyloid Beta Plaque Formation

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Abstract

For decades, mitochondrial dysfunctions and the generation of reactive oxygen species have been proposed to promote the development and progression of the amyloid pathology in Alzheimer’s disease, but this association is still debated. It is unclear whether different mitochondrial dysfunctions, such as oxidative phosphorylation deficiency and oxidative stress, are triggers or rather consequences of the formation of amyloid aggregates. Likewise, the role of the different mitochondrial oxidative phosphorylation complexes in Alzheimer’s patients’ brain remains poorly understood. Previous studies showed that genetic ablation of oxidative phosphorylation enzymes from early age decreased amyloid pathology, which were unexpected results. To better model oxidative phosphorylation defects in aging, we induced the ablation of mitochondrial Complex III (CIIIKO) in forebrain neurons of adult mice with amyloid pathology. We found that mitochondrial Complex III dysfunction in adult neurons induced mild oxidative stress but did not increase amyloid beta accumulation. On the contrary, CIIIKO-AD mice showed decreased plaque number, decreased Aβ42 toxic fragment, and altered amyloid precursor protein clearance pathway. Our results support the hypothesis that mitochondrial dysfunctions alone, caused by oxidative phosphorylation deficiency, is not the cause of amyloid accumulation.

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Data Availability

The complete datasets used and/or analyzed during the current study are available from the corresponding author on request.

Abbreviations

Aβ:

Amyloid beta

AD:

Alzheimer’s disease

APP/PS1:

Amyloid precursor protein (Mo/HuAPP695swe), presenilin 1 (PS1-dE9)

ATP5a:

ATP synthase alpha-subunit gene

BACE1:

Beta-secretase 1, beta-site APP cleaving enzyme 1

BN-PAGE:

Blue native polyacrylamide gel electrophoresis

CaMKIIα:

Calcium/calmodulin-dependent protein kinase II alpha

COX1:

Cyclooxygenase 1 (cytochrome c oxidase)

CS:

Citrate synthase

CTF:

APP C-terminal fragment

CytC:

Cytochrome C

GFAP:

Glial fibrillary acidic protein

Iba1:

Ionized calcium binding adaptor molecule 1

LC3B:

Autophagy marker light chain 3

mtDNA:

Mitochondrial DNA

NDUFB8:

NADH:ubiquinone oxidoreductase subunit B8

NDUFA9:

NADH:ubiquinone oxidoreductase subunit A9

OXPHOS:

Oxidative phosphorylation

PBS:

Phosphate-buffered saline

PFA:

Paraformaldehyde

PGC-1α:

Peroxisome proliferator-activated receptor gamma coactivator 1-alpha

PVDF:

Polyvinylidene difluoride

RISP:

Rieske iron sulfur protein

ROS:

Reactive oxygen species

RT:

Room temperature

SDHA:

Succinate dehydrogenase complex dlavoprotein subunit A

SDS-PAGE:

Sodium dodecyl sulfate polyacrylamide gel electrophoresis

SOD2:

Superoxide dismutase 2

TUJ1:

Neuron-specific class III beta-tubulin

UQCRC1/Core1:

Ubiquinol-cytochrome C reductase core protein 1

UQCRFS1:

Ubiquinol-cytochrome C reductase, Rieske iron-sulfur polypeptide 1

VDAC1/Porin:

Voltage-dependent anion channel

References

  1. Polanco JC et al (2018) Amyloid-beta and tau complexity — towards improved biomarkers and targeted therapies. Nat Rev Neurol 14(1):22–39

    Article  CAS  PubMed  Google Scholar 

  2. Swerdlow RH, Burns JM, Khan SM (2014) The Alzheimer’s disease mitochondrial cascade hypothesis: progress and perspectives. Biochim Biophys Acta 1842(8):1219–1231

    Article  CAS  PubMed  Google Scholar 

  3. Tapias V (2019) Editorial: Mitochondrial Dysfunction and Neurodegeneration. Front Neurosci 13:1372

    Article  PubMed  PubMed Central  Google Scholar 

  4. Hou Y et al (2019) Ageing as a risk factor for neurodegenerative disease. Nat Rev Neurol 15(10):565–581

    Article  PubMed  Google Scholar 

  5. Bowling AC et al (1993) Age-dependent impairment of mitochondrial function in primate brain. J Neurochem 60(5):1964–1967

    Article  CAS  PubMed  Google Scholar 

  6. Hauptmann S et al (2009) Mitochondrial dysfunction: an early event in Alzheimer pathology accumulates with age in AD transgenic mice. Neurobiol Aging 30(10):1574–1586

    Article  CAS  PubMed  Google Scholar 

  7. Hong MG et al (2008) Transcriptome-wide assessment of human brain and lymphocyte senescence. PLoS One 3(8):e3024

    Article  PubMed  PubMed Central  Google Scholar 

  8. Ross JM et al (2010) High brain lactate is a hallmark of aging and caused by a shift in the lactate dehydrogenase A/B ratio. Proc Natl Acad Sci USA 107(46):20087–20092

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Yao J et al (2009) Mitochondrial bioenergetic deficit precedes Alzheimer’s pathology in female mouse model of Alzheimer’s disease. Proc Natl Acad Sci USA 106(34):14670–14675

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Coskun PE, Beal MF, Wallace DC (2004) Alzheimer’s brains harbor somatic mtDNA control-region mutations that suppress mitochondrial transcription and replication. Proc Natl Acad Sci USA 101(29):10726–10731

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Krishnan KJ et al (2012) Mitochondrial DNA deletions cause the biochemical defect observed in Alzheimer’s disease. Neurobiol Aging 33(9):2210–2214

    Article  CAS  PubMed  Google Scholar 

  12. Lin MT et al (2002) High aggregate burden of somatic mtDNA point mutations in aging and Alzheimer’s disease brain. Hum Mol Genet 11(2):133–145

    Article  CAS  PubMed  Google Scholar 

  13. Bennett JP Jr, Keeney PM (2020) Alzheimer’s and Parkinson’s brain tissues have reduced expression of genes for mtDNA OXPHOS Proteins, mitobiogenesis regulator PGC-1alpha protein and mtRNA stabilizing protein LRPPRC (LRP130). Mitochondrion 53:154–157

    Article  CAS  PubMed  Google Scholar 

  14. Chagnon P et al (1995) Distribution of brain cytochrome oxidase activity in various neurodegenerative diseases. NeuroReport 6(5):711–715

    Article  CAS  PubMed  Google Scholar 

  15. Chen JX, Yan SS (2010) Role of mitochondrial amyloid-beta in Alzheimer’s disease. J Alzheimers Dis 20 Suppl 2:S569–S578

    Article  PubMed  Google Scholar 

  16. Long J et al (2012) New evidence of mitochondria dysfunction in the female Alzheimer’s disease brain: deficiency of estrogen receptor-beta. J Alzheimers Dis 30(3):545–558

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Mutisya EM, Bowling AC, Beal MF (1994) Cortical cytochrome oxidase activity is reduced in Alzheimer’s disease. J Neurochem 63(6):2179–2184

    Article  CAS  PubMed  Google Scholar 

  18. Holper L, Ben-Shachar D, Mann JJ (2019) Multivariate meta-analyses of mitochondrial complex I and IV in major depressive disorder, bipolar disorder, schizophrenia, Alzheimer disease, and Parkinson disease. Neuropsychopharmacology 44(5):837–849

    Article  CAS  PubMed  Google Scholar 

  19. Onyango IG, Khan SM, Bennett JP Jr (2017) Mitochondria in the pathophysiology of Alzheimer’s and Parkinson’s diseases. Front Biosci (Landmark Ed) 22:854–872

    Article  CAS  Google Scholar 

  20. Kim SH et al (2000) Decreased levels of complex III core protein 1 and complex V beta chain in brains from patients with Alzheimer’s disease and Down syndrome. Cell Mol Life Sci 57(12):1810–1816

    Article  CAS  PubMed  Google Scholar 

  21. Kenney PM, Bennett JP Jr (2019) Alzheimer’s disease frontal cortex mitochondria show a loss of individual respiratory proteins but preservation of respiratory supercomplexes. Int J Alzheimers Dis 2019:4814783

    PubMed  PubMed Central  Google Scholar 

  22. Fisar Z et al (2019) Activities of mitochondrial respiratory chain complexes in platelets of patients with Alzheimer’s disease and depressive disorder. Mitochondrion 48:67–77

    Article  CAS  PubMed  Google Scholar 

  23. Guglielmotto M et al (2009) The up-regulation of BACE1 mediated by hypoxia and ischemic injury: role of oxidative stress and HIF1alpha. J Neurochem 108(4):1045–1056

    Article  CAS  PubMed  Google Scholar 

  24. Leuner K et al (2012) Mitochondrion-derived reactive oxygen species lead to enhanced amyloid beta formation. Antioxid Redox Signal 16(12):1421–1433

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Paola D et al (2000) Oxidative stress induces increase in intracellular amyloid beta-protein production and selective activation of betaI and betaII PKCs in NT2 cells. Biochem Biophys Res Commun 268(2):642–646

    Article  CAS  PubMed  Google Scholar 

  26. Tamagno E et al (2002) Oxidative stress increases expression and activity of BACE in NT2 neurons. Neurobiol Dis 10(3):279–288

    Article  CAS  PubMed  Google Scholar 

  27. Anandatheerthavarada HK et al (2003) Mitochondrial targeting and a novel transmembrane arrest of Alzheimer’s amyloid precursor protein impairs mitochondrial function in neuronal cells. J Cell Biol 161(1):41–54

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Calkins MJ et al (2011) Impaired mitochondrial biogenesis, defective axonal transport of mitochondria, abnormal mitochondrial dynamics and synaptic degeneration in a mouse model of Alzheimer’s disease. Hum Mol Genet 20(23):4515–4529

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. Casley CS et al (2002) Beta-amyloid inhibits integrated mitochondrial respiration and key enzyme activities. J Neurochem 80(1):91–100

    Article  CAS  PubMed  Google Scholar 

  30. Devi L et al (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(35):9057–9068

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. Hansson Petersen CA et al (2008) The amyloid beta-peptide is imported into mitochondria via the TOM import machinery and localized to mitochondrial cristae. Proc Natl Acad Sci USA 105(35):13145–13150

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. Manczak M et al (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(9):1437–1449

    Article  CAS  PubMed  Google Scholar 

  33. 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(2):45–53

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  34. Wang X et al (2008) Amyloid-beta overproduction causes abnormal mitochondrial dynamics via differential modulation of mitochondrial fission/fusion proteins. Proc Natl Acad Sci USA 105(49):19318–19323

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  35. Fukui H et al (2007) Cytochrome c oxidase deficiency in neurons decreases both oxidative stress and amyloid formation in a mouse model of Alzheimer’s disease. Proc Natl Acad Sci USA 104(35):14163–14168

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  36. Pinto M et al (2013) Mitochondrial DNA damage in a mouse model of Alzheimer’s disease decreases amyloid beta plaque formation. Neurobiol Aging 34(10):2399–2407

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  37. Jankowsky JL et al (2001) Co-expression of multiple transgenes in mouse CNS: a comparison of strategies. Biomol Eng 17(6):157–165

    Article  CAS  PubMed  Google Scholar 

  38. Madisen L et al (2010) A robust and high-throughput Cre reporting and characterization system for the whole mouse brain. Nat Neurosci 13(1):133–140

    Article  CAS  PubMed  Google Scholar 

  39. Waypa GB et al (2013) Superoxide generated at mitochondrial complex III triggers acute responses to hypoxia in the pulmonary circulation. Am J Respir Crit Care Med 187(4):424–432

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  40. Wang J et al (2003) Gender differences in the amount and deposition of amyloidbeta in APPswe and PS1 double transgenic mice. Neurobiol Dis 14(3):318–327

    Article  CAS  PubMed  Google Scholar 

  41. Zhou CN et al (2018) Sex differences in the white matter and myelinated fibers of APP/PS1 mice and the effects of running exercise on the sex differences of AD mice. Front Aging Neurosci 10:243

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  42. Mifflin MA et al (2021) Sex differences in the IntelliCage and the Morris water maze in the APP/PS1 mouse model of amyloidosis. Neurobiol Aging 101:130–140

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  43. Dominguez S et al (2020) Sex differences in the phosphoproteomic profiles of APP/PS1 mice after chronic unpredictable mild stress. J Alzheimers Dis 74(4):1131–1142

    Article  CAS  PubMed  Google Scholar 

  44. Li X et al (2016) Sex differences between APPswePS1dE9 mice in A-beta accumulation and pancreatic islet function during the development of Alzheimer’s disease. Lab Anim 50(4):275–285

    Article  CAS  PubMed  Google Scholar 

  45. Schmittgen TD, Livak KJ (2008) Analyzing real-time PCR data by the comparative C(T) method. Nat Protoc 3(6):1101–1108

    Article  CAS  PubMed  Google Scholar 

  46. Barrientos A, Fontanesi F, Diaz F (2009) Evaluation of the mitochondrial respiratory chain and oxidative phosphorylation system using polarography and spectrophotometric enzyme assays. Curr Protoc Hum Genet Chapter 19:Unit19 3

    PubMed  Google Scholar 

  47. Jankowsky JL et al (2004) Mutant presenilins specifically elevate the levels of the 42 residue beta-amyloid peptide in vivo: evidence for augmentation of a 42-specific gamma secretase. Hum Mol Genet 13(2):159–170

    Article  CAS  PubMed  Google Scholar 

  48. Choi CI et al (2014) Simultaneous deletion of floxed genes mediated by CaMKIIalpha-Cre in the brain and in male germ cells: application to conditional and conventional disruption of Goalpha. Exp Mol Med 46:e93

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  49. Jones KJ et al (2018) Rapid, experience-dependent translation of neurogranin enables memory encoding. Proc Natl Acad Sci USA 115(25):E5805–E5814

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  50. Garrido-Garcia A et al (2019) Neurogranin expression is regulated by synaptic activity and promotes synaptogenesis in cultured hippocampal neurons. Mol Neurobiol 56(11):7321–7337

    Article  CAS  PubMed  Google Scholar 

  51. Mohajeri MH, Saini KD, Nitsch RM (2004) Transgenic BACE expression in mouse neurons accelerates amyloid plaque pathology. J Neural Transm (Vienna) 111(3):413–425

    Article  CAS  Google Scholar 

  52. Li R et al (2004) Amyloid beta peptide load is correlated with increased beta-secretase activity in sporadic Alzheimer’s disease patients. Proc Natl Acad Sci USA 101(10):3632–3637

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  53. Kaspar S, Oertlin C, Szczepanowska K, Kukat A, Senft K, Lucas C, Brodesser S, Hatzoglou M, Larsson O, Topisirovic I, Trifunovic A (2021) Adaptation to mitochondrial stress requires CHOP-directed tuning of ISR. Sci Adv 7(22)

  54. Misrani A, Tabassum S, Yang L (2021) Mitochondrial dysfunction and oxidative stress in Alzheimer’s disease. Front Aging Neurosci 13:617588

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  55. Diaz F et al (2012) A defect in the mitochondrial complex III, but not complex IV, triggers early ROS-dependent damage in defined brain regions. Hum Mol Genet 21(23):5066–5077

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  56. Sheng B et al (2012) Impaired mitochondrial biogenesis contributes to mitochondrial dysfunction in Alzheimer’s disease. J Neurochem 120(3):419–429

    Article  CAS  PubMed  Google Scholar 

  57. Terada T et al (2021) Mitochondrial complex I abnormalities is associated with tau and clinical symptoms in mild Alzheimer’s disease. Mol Neurodegener 16(1):28

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  58. Peralta S, Pinto M, Arguello T , Garcia S, Diaz F, Moraes CT (2020) Metformin delays neurological symptom onset in a mouse model of neuronal complex I deficiency. JCI Insight 5(21) 

  59. Pickrell AM et al (2011) The striatum is highly susceptible to mitochondrial oxidative phosphorylation dysfunctions. J Neurosci 31(27):9895–9904

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  60. Zhang L et al (2015) Modulation of mitochondrial complex I activity averts cognitive decline in multiple animal models of familial Alzheimer’s Disease. EBioMedicine 2(4):294–305

    Article  PubMed  PubMed Central  Google Scholar 

  61. Kukreja L et al (2014) Increased mtDNA mutations with aging promotes amyloid accumulation and brain atrophy in the APP/Ld transgenic mouse model of Alzheimer’s disease. Mol Neurodegener 9:16

    Article  PubMed  PubMed Central  Google Scholar 

  62. Virtuoso A, Colangelo AM, Maggio N, Fennig U, Weinberg N, Papa M, De Luca C (2021) The spatiotemporal coupling: regional energy failure and aberrant proteins in neurodegenerative diseases. Int J Mol Sci 22(21)

  63. Mouton-Liger F et al (2012) Oxidative stress increases BACE1 protein levels through activation of the PKR-eIF2alpha pathway. Biochim Biophys Acta 1822(6):885–896

    Article  CAS  PubMed  Google Scholar 

  64. Tamagno E et al (2008) Oxidative stress activates a positive feedback between the gamma- and beta-secretase cleavages of the beta-amyloid precursor protein. J Neurochem 104(3):683–695

    CAS  PubMed  Google Scholar 

  65. Lopez Sanchez MIG et al (2017) Amyloid precursor protein drives down-regulation of mitochondrial oxidative phosphorylation independent of amyloid beta. Sci Rep 7(1):9835

    Article  PubMed  PubMed Central  Google Scholar 

  66. Mao P et al (2012) Mitochondria-targeted catalase reduces abnormal APP processing, amyloid beta production and BACE1 in a mouse model of Alzheimer’s disease: implications for neuroprotection and lifespan extension. Hum Mol Genet 21(13):2973–2990

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  67. McManus MJ, Murphy MP, Franklin JL (2011) The mitochondria-targeted antioxidant MitoQ prevents loss of spatial memory retention and early neuropathology in a transgenic mouse model of Alzheimer’s disease. J Neurosci 31(44):15703–15715

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  68. Ross JM, Olson L, Coppotelli G (2015) Mitochondrial and ubiquitin proteasome system dysfunction in ageing and disease: two sides of the same coin? Int J Mol Sci 16(8):19458–19476

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  69. Huang Q et al (2013) Negative regulation of 26S proteasome stability via calpain-mediated cleavage of Rpn10 subunit upon mitochondrial dysfunction in neurons. J Biol Chem 288(17):12161–12174

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  70. Meul T et al (2020) Mitochondrial regulation of the 26S proteasome. Cell Rep 32(8):108059

    Article  CAS  PubMed  Google Scholar 

  71. Livnat-Levanon N et al (2014) Reversible 26S proteasome disassembly upon mitochondrial stress. Cell Rep 7(5):1371–1380

    Article  CAS  PubMed  Google Scholar 

  72. Hohn A, Konig J, Grune T (2013) Protein oxidation in aging and the removal of oxidized proteins. J Proteomics 92:132–159

    Article  PubMed  Google Scholar 

  73. Adav SS, Park JE, Sze SK (2019) Quantitative profiling brain proteomes revealed mitochondrial dysfunction in Alzheimer’s disease. Mol Brain 12(1):8

    Article  PubMed  PubMed Central  Google Scholar 

  74. Crouch PJ et al (2006) Copper-dependent inhibition of cytochrome c oxidase by Abeta(1–42) requires reduced methionine at residue 35 of the Abeta peptide. J Neurochem 99(1):226–236

    Article  CAS  PubMed  Google Scholar 

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Funding

This work was supported primarily by the Florida Biomedical Foundation Ed and Ethel Moore Alzheimer’s Disease Research Program grant 5AZ06 (CTM), the National Institute of Health Grants K01AG057815 (MP), and 1R01NS079965 (CTM). The following grants also helped support this work: NIH grants 5R01EY010804, 1R01AG036871, R33ES025673, and the Muscular Dystrophy Association.

Author information

Authors and Affiliations

  1. Department of Neurology, University of Miami Miller School of Medicine, Miami, FL, USA

    Milena Pinto, Francisca Diaz, Nadee Nissanka & Carlos T. Moraes

  2. The Miami Project to Cure Paralysis, Department of Neurological Surgery, University of Miami Miller School of Medicine, Miami, FL, USA

    Chelsey S. Guastucci, Placido Illiano & Roberta Brambilla

Authors
  1. Milena Pinto
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  2. Francisca Diaz
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  3. Nadee Nissanka
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  4. Chelsey S. Guastucci
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  5. Placido Illiano
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  6. Roberta Brambilla
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  7. Carlos T. Moraes
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Contributions

MP designed the research, performed the experiments, analyzed, and interpreted data, and wrote the manuscript. FD performed BN-PAGE analysis, enzymatic activity, and contributed intellectually to the research. NN performed qPCR analysis. CSG and PI assisted in plaque counting. RB contributed intellectually to the research. CTM planned the project together with MP and contributed to the writing of the manuscript. All authors read and approved the final manuscript. Francisca Diaz and Placido Illiano passed away before the submission of the manuscript.

Corresponding authors

Correspondence to Milena Pinto or Carlos T. Moraes.

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All experiments and animal husbandry were performed according to a protocol approved by the University of Miami Institutional Animal Care and Use Committee.

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Francisca Diaz deceased in March 2021.

Placido Illiano deceased in February 2022.

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Pinto, M., Diaz, F., Nissanka, N. et al. Adult-Onset Deficiency of Mitochondrial Complex III in a Mouse Model of Alzheimer’s Disease Decreases Amyloid Beta Plaque Formation. Mol Neurobiol 59, 6552–6566 (2022). https://doi.org/10.1007/s12035-022-02992-3

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