Oxidative stress and amyloid-beta pathology in normal individuals with a maternal history of Alzheimer's

Biol Psychiatry. 2010 Nov 15;68(10):913-21. doi: 10.1016/j.biopsych.2010.07.011.

Abstract

Background: Epidemiology and imaging studies showed that cognitively normal (NL) individuals with a maternal history (MH) of late-onset Alzheimer's disease (LOAD) might be at increased risk for Alzheimer's disease (AD) compared with NL with a paternal history (PH) and NL with a negative family history of LOAD (NH). With a panel of cerebrospinal fluid (CSF) markers, this study examined whether NL MH showed evidence for AD pathology compared with PH and NH.

Methods: Fifty-nine 40-80-year-old NL subjects were examined, including 23 MH and 14 PH whose parents had a clinician-certified diagnosis of LOAD and 22 NH. All subjects completed clinical neuropsychological examinations and a lumbar puncture to measure CSF levels of amyloid-beta (Aβ(40), Aβ(42), Aβ(42/40)), total and hyperphosphorylated tau (T-Tau and P-Tau(231); markers of axonal degeneration and neurofibrillary tangles, respectively), and F₂-isoprostanes (IsoP) (a marker of oxidative stress).

Results: Groups were comparable for demographic and neuropsychological measures. The MH subjects showed higher IsoP and reduced Aβ(42/40) CSF levels compared with NH and with PH (p values ≤ .05), whereas no differences were found between NH and PH. No group differences were found for P-Tau(231) and T-Tau. The IsoP and Aβ(42/40) levels were correlated only within the MH group (R² = .32, p = .005) and discriminated MH from the other subjects with 70% accuracy (relative risk = 3.7%, 95% confidence interval = 1.6-9.7, p < .001). Results remained significant controlling for age, gender, education, and apolipoprotein E genotype.

Conclusions: Adult children of LOAD-affected mothers express a pathobiological phenotype characterized by Aβ-associated oxidative stress consistent with AD, which might reflect increased risk for developing the disease.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Alzheimer Disease / cerebrospinal fluid
  • Alzheimer Disease / genetics*
  • Amyloid beta-Peptides / cerebrospinal fluid*
  • Biomarkers / cerebrospinal fluid
  • F2-Isoprostanes / cerebrospinal fluid
  • Family Health*
  • Female
  • Genetic Predisposition to Disease
  • Humans
  • Male
  • Middle Aged
  • Mothers
  • Oxidative Stress*
  • tau Proteins / cerebrospinal fluid

Substances

  • Amyloid beta-Peptides
  • Biomarkers
  • F2-Isoprostanes
  • tau Proteins