Faculty Collaboration Database

Reduced mitochondria cytochrome oxidase activity in adult children of mothers with Alzheimer's disease. J Alzheimers Dis 2011;27(3):483-90

Date

08/16/2011

Pubmed ID

21841246

Pubmed Central ID

PMC3291954

DOI

10.3233/JAD-2011-110866

Scopus ID

2-s2.0-80055088009 (requires institutional sign-in at Scopus site)   79 Citations

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.

Author List

Mosconi L, de Leon M, Murray J, E L, Lu J, Javier E, McHugh P, Swerdlow RH

Author

Lezi E PhD Assistant Professor in the Cell Biology, Neurobiology and Anatomy department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Adult
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