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Reduced mitochondria cytochrome oxidase activity in adult children of mothers with Alzheimer's disease.

TitleReduced mitochondria cytochrome oxidase activity in adult children of mothers with Alzheimer's disease.
Publication TypeJournal Article
Year of Publication2011
AuthorsMosconi L, de Leon M, Murray J, E L, Lu J, Javier E, McHugh P, Swerdlow RH
JournalJ Alzheimers Dis
Volume27
Issue3
Pagination483-90
Date Published2011
ISSN1875-8908
KeywordsAdult, Age of Onset, Aged, Alzheimer Disease, Biomarkers, Blood Platelets, Cohort Studies, Down-Regulation, Electron Transport Complex IV, Enzyme Activation, Female, Genetic Predisposition to Disease, Humans, Male, Middle Aged, Mitochondria, Mothers, Sex Factors
Abstract

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.

DOI10.3233/JAD-2011-110866
Alternate JournalJ. Alzheimers Dis.
PubMed ID21841246
PubMed Central IDPMC3291954
Grant ListR01 AG022374 / AG / NIA NIH HHS / United States
M01 RR000096 / RR / NCRR NIH HHS / United States
R01 AG035137 / AG / NIA NIH HHS / United States
AG035137 / AG / NIA NIH HHS / United States
R21 AG032554 / AG / NIA NIH HHS / United States
R01 AG013616 / AG / NIA NIH HHS / United States
P30 AG035982 / AG / NIA NIH HHS / United States
UL1 RR029893 / RR / NCRR NIH HHS / United States
P30 AG008051 / AG / NIA NIH HHS / United States
P30 AG008051-16S1 / AG / NIA NIH HHS / United States
AG008051 / AG / NIA NIH HHS / United States
AG022374 / AG / NIA NIH HHS / United States
P30AG035982 / AG / NIA NIH HHS / United States
AG032554 / AG / NIA NIH HHS / United States
R01 AG035137-03 / AG / NIA NIH HHS / United States
R01 AG022374-08 / AG / NIA NIH HHS / United States
AG13616 / AG / NIA NIH HHS / United States
M01RR0096 / RR / NCRR NIH HHS / United States
R01 AG013616-20 / AG / NIA NIH HHS / United States
RR029893 / RR / NCRR NIH HHS / United States
M01 RR000096-42 / RR / NCRR NIH HHS / United States
R21 AG032554-02 / AG / NIA NIH HHS / United States

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