Reduced mitochondria cytochrome oxidase activity in adult children of mothers with Alzheimer's disease.
Level 4 - case-series / case-control
Cross-sectional comparative study with small convenience groups
PubMed 21841246 · doi:10.3233/JAD-2011-110866
What was done
Researchers measured platelet mitochondrial cytochrome oxidase (COX, complex IV) activity from blood draws in 36 cognitively normal adults (mean age 55 ± 15 years, range 27–71, 56% female, CDR = 0, MMSE ≥ 28, 28% APOE-4 carriers). Participants were divided into three groups of 12: those with a maternal history of late-onset Alzheimer's disease (MH), paternal history (PH), or negative family history (NH). Citrate synthase (CS) activity was measured as a reference standard.
What was found
After correcting for CS, platelet COX activity was 29% lower in the MH group compared to the NH group, and 30% lower compared to the PH group (p ≤ 0.006). Findings remained significant after adjusting for age, gender, education, and APOE status. No differences in COX activity were observed between the PH and NH groups. COX activity discriminated MH from the other groups with ≥75% accuracy and relative risk ≥3 (p ≤ 0.005).
Why it matters
Because mitochondrial DNA is exclusively maternally inherited, the selective reduction of mitochondrial complex IV activity in offspring of affected mothers suggests a potential maternally transmitted mitochondrial mechanism in late-onset Alzheimer's risk.
Limits
The study is limited by a very small sample size (n = 36 total, 12 per group), a cross-sectional design, reliance on peripheral platelet surrogates rather than brain tissue, and an absence of longitudinal follow-up to assess actual progression to cognitive impairment.
Cited by
- supports Risk for mental health disorders, Parkinson's disease, and Alzheimer's disease shows stronger maternal than paternal inheritance.