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Oxidative stress and amyloid-beta pathology in normal individuals with a maternal history of Alzheimer's.

TitleOxidative stress and amyloid-beta pathology in normal individuals with a maternal history of Alzheimer's.
Publication TypeJournal Article
Year of Publication2010
AuthorsMosconi L, Glodzik L, Mistur R, McHugh P, Rich KE, Javier E, Williams S, Pirraglia E, De Santi S, Mehta PD, Zinkowski R, Blennow K, Pratico D, de Leon MJ
JournalBiol Psychiatry
Volume68
Issue10
Pagination913-21
Date Published2010 Nov 15
ISSN1873-2402
KeywordsAdult, Aged, Aged, 80 and over, Alzheimer Disease, Amyloid beta-Peptides, Biomarkers, F2-Isoprostanes, Family Health, Female, Genetic Predisposition to Disease, Humans, Male, Middle Aged, Mothers, Oxidative Stress, tau Proteins
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.

DOI10.1016/j.biopsych.2010.07.011
Alternate JournalBiol. Psychiatry
PubMed ID20817151
PubMed Central IDPMC2967599
Grant ListR01 AG022374 / AG / NIA NIH HHS / United States
M01 RR000096 / RR / NCRR NIH HHS / United States
R01 AG035137 / AG / NIA NIH HHS / United States
M01 RR000096-478509 / RR / NCRR NIH HHS / United States
R21 AG032554 / AG / NIA NIH HHS / United States
R01 AG013616 / AG / NIA NIH HHS / United States
M01 RR000096-478521 / RR / NCRR NIH HHS / United States
P30 AG008051 / AG / NIA NIH HHS / United States
R01 AG012101 / AG / NIA NIH HHS / United States
AG022374 / AG / NIA NIH HHS / United States
R01 AG012101-15S1 / AG / NIA NIH HHS / United States
AG032554 / AG / NIA NIH HHS / United States
AG13616 / AG / NIA NIH HHS / United States
M01RR0096 / RR / NCRR NIH HHS / United States
R01 AG013616-20 / AG / NIA NIH HHS / United States
AG08051 / AG / NIA NIH HHS / United States
R21 AG032554-02 / AG / NIA NIH HHS / United States
R01 AG022374-05 / AG / NIA NIH HHS / United States
AG12101 / AG / NIA NIH HHS / United States

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