Reduced mitochondria cytochrome oxidase activity in adult children of mothers with Alzheimer's disease
Open accessAbstract
Biomarker studies demonstrate inheritance of glucose hypometabolism and increased amyloid-β deposition in adult offspring of mothers, but not fathers, affected by late-onset Alzheimer's disease (LOAD). The underlying genetic mechanisms are unknown. We investigated whether cognitively normal (NL) individuals with a maternal history of LOAD (MH) have reduced platelet mitochondrial cytochrome oxidase activity (COX, electron transport chain complex IV) compared to those with paternal (PH) or negative family history (NH). Thirty-six consecutive NL individuals (age 55 ± 15 y, range 27-71 y, 56% female, CDR = 0, MMSE ≥28, 28% APOE-4 carriers), including 12 NH, 12 PH, and 12 MH, received a blood draw to measure platelet mitochondrial COX activity. Citrate synthase activity (CS) was measured as a reference. Groups were comparable for clinical and neuropsychological measures. We found that after correcting for CS, COX activity was reduced by 29% in MH compared to NH, and by 30% in MH compared to PH (p ≤ 0.006). Results remained significant controlling for age, gender, education, and APOE. No differences were found between PH and NH. COX measures discriminated MH from the other groups with accuracy ≥75%, and relative risk ≥3 (p ≤ 0.005). Among NL with LOAD-parents, only those with MH showed reduced COX activity in platelet mitochondria compared to PH and NH. The association between maternal history of LOAD and systemic COX reductions suggests transmission via mitochondrial DNA, which is exclusively maternally inherited in humans.
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Mean COX activity was lower in cognitively normal adult children of AD-affected mothers than in those with AD-affected fathers or unaffected parents.
“Mean COX activity was lower in subjects with AD-affected mothers than it was in the other two groups.”
From The Alzheimer’s disease mitochondrial cascade hypothesis: progress and perspectives (2014) · cites this paper as [142]
Cognitively normal, middle-aged individuals with AD mothers have relatively low platelet COX activities.
“Cognitively normal, middle-aged individuals with AD mothers, who have a higher risk of developing AD than middle aged individuals with AD fathers or no AD-affected parents [131], have relatively low platelet COX activities [132].”
From Brain aging, Alzheimer's disease, and mitochondria (2011) · cites this paper as [132]
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- Authors
- Mosconi, L., de Leon, M., Murray, J., E, L., Lu, J., Javier, E., McHugh, P., & Swerdlow, R. H.
- Affiliations
- New York University (US)
- New York University School of Medicine, New York, NY, USA
- University of Kansas School of Medicine, Kansas City, KS, USA
- University of Kansas (US)
- Corresponding author
- Mosconi, Lisa
- Venue
- Journal of Alzheimer s Disease
- Publisher
- SAGE Publications
- Published
- 2011-11-29
- Volume
- 27
- Issue
- 3
- Pages
- 483-490
- ISSN
- 1387-2877 (ISSN-L)
- 1875-8908
- PMC
- PMC3291954
- OpenAlex
- W1600031243
- Cited by
- 97
- References
- 41
- Citations by year
- 2026: 3 · 2025: 6 · 2024: 1 · 2023: 6 · 2022: 10 · 2021: 5 · 2020: 11 · 2019: 4 · 2018: 6 · 2017: 12 · 2016: 4 · 2015: 5 · 2014: 7 · 2013: 7 · 2012: 6
- FWCI
- 5.23
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Journal of Alzheimer s Disease (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institute on Aging (AG035137, AG008051, AG022374, R01AG022374, P30AG008051, AG032554, R21AG032554, P30AG035982, R01AG013616, R01AG035137, AG 13616)
- National Center for Research Resources (M01RR0096, UL1RR029893, M01RR000096, RR029893)
- 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, maternal inheritance
- MeSH terms
- Adult, Aged, Alzheimer Disease, Blood Platelets, Electron Transport Complex IV, Enzyme Activation, Female, Humans, Male, Middle Aged, Mitochondria, Mothers, Sex Factors, Cohort Studies, Biomarkers, Down-Regulation, Age of Onset, Genetic Predisposition to Disease
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