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 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 (A beta(40), A beta(42) A beta(42/40)) total and hyperphosphorylated tau (T Tau and P-Tau(231) markers of axonal degeneration and neurofibrillary tangles respectively) and F-2 isoprostanes (IsoP) (a marker of oxidative stress) Results Groups were comparable for demographic and neuropsychological measures The MH subjects showed higher IsoP and reduced A beta(42/40) CSF levels compared with NH and with PH (p value <= 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 A beta(42/40) levels were correlated only within the MH group (R-2 = 32 p = 005) and discriminated MH from the other subjects with 70% accuracy (relative risk = 37% 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 A beta associated oxidative stress consistent with AD which might reflect increased risk for developing the disease