title: Oxidative stress and amyloid-beta pathology in normal individuals with a maternal history of Alzheimer's.
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.
authors.affiliation: Center for Brain Health, Department of Psychiatry, New York University School of Medicine, New York, New York 10016, USA. lisa.mosconi@nyumc.org
authors.forename: Lisa
authors.initials: L
authors.lastname: Mosconi
authors.forename: Lidia
authors.initials: L
authors.lastname: Glodzik
authors.forename: Rachel
authors.initials: R
authors.lastname: Mistur
authors.forename: Pauline
authors.initials: P
authors.lastname: McHugh
authors.forename: Kenneth E
authors.initials: KE
authors.lastname: Rich
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Javier
authors.forename: Schantel
authors.initials: S
authors.lastname: Williams
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Pirraglia
authors.forename: Susan
authors.initials: S
authors.lastname: De Santi
authors.forename: Pankaj D
authors.initials: PD
authors.lastname: Mehta
authors.forename: Raymond
authors.initials: R
authors.lastname: Zinkowski
authors.forename: Kaj
authors.initials: K
authors.lastname: Blennow
authors.forename: Domenico
authors.initials: D
authors.lastname: Pratico
authors.forename: Mony J
authors.initials: MJ
authors.lastname: de Leon
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000134:cerebrospinal fluid / Q000235:genetics*; D016229:Amyloid beta-Peptides / Q000134:cerebrospinal fluid*; D015415:Biomarkers / Q000134:cerebrospinal fluid; D028441:F2-Isoprostanes / Q000134:cerebrospinal fluid; D005192:Family Health; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D008297:Male; D008875:Middle Aged; D009035:Mothers; D018384:Oxidative Stress; D016875:tau Proteins / Q000134:cerebrospinal fluid
chemical_list: D016229:Amyloid beta-Peptides; D015415:Biomarkers; D028441:F2-Isoprostanes; D016875:tau Proteins
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