Oxidative stress and amyloid-beta pathology in normal individuals with a maternal history of Alzheimer's
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 4080-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 (Aβ40, Aβ42, Aβ42/40), total and hyperphosphorylated tau (T-Tau and P-Tau231; 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 Aβ42/40CSF 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-Tau231and T-Tau. The IsoP and Aβ42/40levels 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 = 1.69.7, 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.