title: Prevalence of Alzheimer's pathologic endophenotypes in asymptomatic and mildly impaired first-degree relatives.
abstract: OBJECTIVE
  A positive family history (FH) is a risk factor for late-onset Alzheimer's disease (AD). Our aim was to examine the effects of FH on pathological and neuronal loss biomarkers across the cognitive spectrum.
  
  
  METHODS
  Cross-sectional analyses of data from a national biomarker study.
  
  
  METHODS
  The Alzheimer's Disease Neuroimaging Initiative national study.
  
  
  METHODS
  257 subjects (ages 55-89), divided into cognitively normal (CN), mild cognitive impairment (MCI), and AD groups, with CSF and FH data.
  
  
  METHODS
  Cerebrospinal fluid (CSF) Aβ42, tau, and tau/Aβ42 ratio, MRI-measured hippocampal volumes.
  
  
  METHODS
  Univariate and multivariate analyses.
  
  
  RESULTS
  In MCI, CSF Aβ42 was lower (p = .005), t-tau was higher (p = 0.02) and t-tau/Aβ42 ratio was higher (p = 0.002) in FH+ than FH- subjects. A significant residual effect of FH on pathologic markers in MCI remained after adjusting for ApoE4 (p<0.05). Among CN, 47% of FH+ exhibited "pathologic signature of AD" (CSF t-tau/Aβ42 ratio >0.39) versus 21% of FH- controls (p = 0.03). The FH effect was not significant in AD subjects. Hippocampal and intracranial volumes did not differ between FH+ and FH- subjects in any group.
  
  
  CONCLUSIONS
  A positive family history of late-onset AD is associated with a higher prevalence of an abnormal cerebral beta-amyloid and tau protein phenotype in MCI. The unexplained genetic heritability in family history is about the half the size of the ApoE4 effect. Longitudinal studies are warranted to more definitively examine this issue.
authors.affiliation: Department of Psychiatry, Duke University Medical Center, Durham, North Carolina, United States of America.
authors.forename: Erika J
authors.initials: EJ
authors.lastname: Lampert
authors.forename: Kingshuk
authors.initials: K
authors.lastname: Roy Choudhury
authors.forename: Christopher A
authors.initials: CA
authors.lastname: Hostage
authors.forename: Jeffrey R
authors.initials: JR
authors.lastname: Petrella
authors.forename: P Murali
authors.initials: PM
authors.lastname: Doraiswamy
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000134:cerebrospinal fluid / Q000453:epidemiology* / Q000473:pathology*; D016229:Amyloid beta-Peptides / Q000134:cerebrospinal fluid; D053327:Apolipoprotein E4 / Q000378:metabolism; D058070:Asymptomatic Diseases / Q000453:epidemiology*; D015415:Biomarkers / Q000134:cerebrospinal fluid; D060825:Cognitive Dysfunction / Q000134:cerebrospinal fluid / Q000453:epidemiology*; D058068:Endophenotypes / Q000134:cerebrospinal fluid; D005190:Family; D006624:Hippocampus / Q000473:pathology; D006801:Humans; D008875:Middle Aged; D009929:Organ Size; D015995:Prevalence; D012372:ROC Curve; D016875:tau Proteins / Q000134:cerebrospinal fluid
chemical_list: D016229:Amyloid beta-Peptides; D053327:Apolipoprotein E4; D015415:Biomarkers; D016875:tau Proteins