Oxidative stress and amyloid-beta pathology in normal individuals with a maternal history of Alzheimer's.
| Publication Type | Academic Article |
| Authors | Mosconi L, Glodzik L, Mistur R, McHugh P, Rich K, Javier E, Williams S, Pirraglia E, De Santi S, Mehta P, Zinkowski R, Blennow K, Pratico D, de Leon M |
| Journal | Biol Psychiatry |
| Volume | 68 |
| Issue | 10 |
| Pagination | 913-21 |
| Date Published | 11/15/2010 |
| ISSN | 1873-2402 |
| Keywords | Alzheimer Disease, Amyloid beta-Peptides, Family Health, Oxidative Stress |
| 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. |
| DOI | 10.1016/j.biopsych.2010.07.011 |
| PubMed ID | 20817151 |
| PubMed Central ID | PMC2967599 |