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Oxidative Stress and Amyloid-Beta Pathology in Normal Individuals with A Maternal History of Alzheimer's

Published:September 06, 2010DOI:https://doi.org/10.1016/j.biopsych.2010.07.011

      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 (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 Aβ42/40 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-Tau231 and T-Tau. The IsoP and Aβ42/40 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.

      Key Words

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