title: Reduced mitochondria cytochrome oxidase activity in adult children of mothers with Alzheimer's disease.
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.
authors.affiliation: Center for Brain Health, Department of Psychiatry, New York University School of Medicine, New York, NY 10016, USA. lisa.mosconi@nyumc.org
authors.forename: Lisa
authors.initials: L
authors.lastname: Mosconi
authors.forename: Mony
authors.initials: M
authors.lastname: de Leon
authors.forename: John
authors.initials: J
authors.lastname: Murray
authors.forename: Lezi
authors.initials: L
authors.lastname: E
authors.forename: Jianghua
authors.initials: J
authors.lastname: Lu
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Javier
authors.forename: Pauline
authors.initials: P
authors.lastname: McHugh
authors.forename: Russell H
authors.initials: RH
authors.lastname: Swerdlow
mesh_terms: D000328:Adult; D017668:Age of Onset; D000368:Aged; D000544:Alzheimer Disease / Q000201:enzymology* / Q000235:genetics / Q000473:pathology; D015415:Biomarkers / Q000097:blood; D001792:Blood Platelets / Q000201:enzymology; D015331:Cohort Studies; D015536:Down-Regulation / Q000235:genetics*; D003576:Electron Transport Complex IV / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D004789:Enzyme Activation / Q000235:genetics; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D008297:Male; D008875:Middle Aged; D008928:Mitochondria / Q000201:enzymology* / Q000473:pathology; D009035:Mothers; D012737:Sex Factors
chemical_list: D015415:Biomarkers; D003576:Electron Transport Complex IV