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Cited by 51Alzheimer's disease research and treatmentsMitochondrial Function and PathologyDementia and Cognitive Impairment Research

Mitochondrial function and Aβ in Alzheimer's disease postmortem brain

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Troutwine, Benjamin R., Strope, Taylor A., Franczak, Edziu, Lysaker, Colton R., Hamid, Laylan, Mansel, Clayton, Stopperan, Julia A., Gouvion, Cynthia M. +3 more·2022·Neurobiology of Disease
DOI 10.1016/j.nbd.2022.105781PMC PMC9329272
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Abstract

INTRODUCTION: Mitochondrial dysfunction is observed in Alzheimer's disease (AD). However, the relationship between functional mitochondrial deficits and AD pathologies is not well established in human subjects. METHODS: Post-mortem human brain tissue from 11 non-demented (ND) and 12 AD subjects was used to examine mitochondrial electron transport chain (ETC) function. Data were analyzed by neuropathology diagnosis and Apolipoprotein E (APOE) genotype. Relationships between AD pathology and mitochondrial function were determined. RESULTS: AD subjects had reductions in brain cytochrome oxidase (COX) function and complex II Vmax. APOE ε4 carriers had COX, complex II and III deficits. AD subjects had reduced expression of Complex I-III ETC proteins, no changes were observed in APOE ε4 carriers. No correlation between p-Tau Thr 181 and mitochondrial outcomes was observed, although brains from non-demented subjects demonstrated positive correlations between Aβ concentration and COX Vmax. DISCUSSION: These data support a dysregulated relationship between brain mitochondrial function and Aβ pathology in AD.

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  • Postmortem AD brain from APOE4 carriers displays mitochondrial dysfunction and increased oxidative stress markers.

    “Work from our group and others show that postmortem AD brain from APOE4 carriers display mitochondrial dysfunction and increased oxidative stress markers 15,16 .”

    From APOE4-drives brain bioenergetic shifts independent of Alzheimer’s disease pathology (2026) · cites this paper as [16]

    The Results report mitochondrial respiratory-chain deficits in postmortem brain from APOE ε4 carriers, but the carrier analysis combined AD and non-demented subjects; it did not establish the finding specifically within AD carriers. The Introduction mentions increased reactive oxygen species in AD research generally, but the paper does not report increased oxidative-stress markers in postmortem AD brain from APOE ε4 carriers. (LLM, conf=0.88)

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Authors
Troutwine, B. R., Strope, T. A., Franczak, E., Lysaker, C. R., Hamid, L., Mansel, C., Stopperan, J. A., Gouvion, C. M., Haeri, M., Swerdlow, R. H., & Wilkins, H. M.
Affiliations
  • University of Kansas (US)
  • University of Kansas Medical Center (US)
Corresponding author
Wilkins, Heather M.
ORCID
Venue
Neurobiology of Disease
Publisher
Elsevier BV
Published
2022-09
Volume
171
Pages
105781
ISSN
0969-9961 (ISSN-L)
DOI
10.1016/j.nbd.2022.105781
PMC
PMC9329272
OpenAlex
W4281724038
Cited by
51
References
10
Citations by year
2026: 18 · 2025: 12 · 2024: 8 · 2023: 8 · 2022: 2 · 2016: 1 · 2015: 1 · 2013: 1
FWCI
4.53
Type
journal article
Language
en
Open access
Licence
Locations
  • Neurobiology of Disease (publishedVersion, cc-by-nc-nd)
  • PubMed (publishedVersion)
  • PubMed Central (acceptedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Funders
National Institute on Aging (R00AG056600, P30AG035982, P30AG072973, T32AG078114)
Topics
  • Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Mitochondrial Function and Pathology
  • Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
Keywords
Alzheimer's disease, mitochondrial dysfunction, electron transport chain, amyloid-beta, cytochrome c oxidase, complex II, APOE ε4, postmortem brain, tau phosphorylation, mitochondrial protein expression
MeSH terms
Alzheimer Disease, Autopsy, Brain, Electron Transport Complex IV, Humans, Mitochondria, Amyloid beta-Peptides, Apolipoprotein E4

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