Biological psychiatry · 2010
Oxidative stress and amyloid-beta pathology in normal individuals with a maternal history of Alzheimer's.
СтатьяПоддержка NIH: внешняя программаПоддержка исследования: вне правительства СШАНазвание и аннотация: Перевод пока не подготовлен
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Mosconi Lisa, Glodzik Lidia, Mistur Rachel, McHugh Pauline, Rich Kenneth E, Javier Elizabeth, Williams Schantel, Pirraglia Elizabeth, De Santi Susan, Mehta Pankaj D, Zinkowski Raymond, Blennow Kaj, Pratico Domenico, de Leon Mony J
Аннотация
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.
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.