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Prevalence of Alzheimer's pathologic endophenotypes in asymptomatic and mildly impaired first-degree relatives.

Publication ,  Journal Article
Lampert, EJ; Roy Choudhury, K; Hostage, CA; Petrella, JR; Doraiswamy, PM; Alzheimer’s Disease Neuroimaging Initiative,
Published in: PLoS One
2013

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. DESIGN: Cross-sectional analyses of data from a national biomarker study. SETTING: The Alzheimer's Disease Neuroimaging Initiative national study. PATIENTS: 257 subjects (ages 55-89), divided into cognitively normal (CN), mild cognitive impairment (MCI), and AD groups, with CSF and FH data. OUTCOME MEASURES: Cerebrospinal fluid (CSF) Aβ42, tau, and tau/Aβ42 ratio, MRI-measured hippocampal volumes. STATISTICS: 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.

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Published In

PLoS One

DOI

EISSN

1932-6203

Publication Date

2013

Volume

8

Issue

4

Start / End Page

e60747

Location

United States

Related Subject Headings

  • tau Proteins
  • ROC Curve
  • Prevalence
  • Organ Size
  • Middle Aged
  • Humans
  • Hippocampus
  • General Science & Technology
  • Family
  • Endophenotypes
 

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Lampert, E. J., Roy Choudhury, K., Hostage, C. A., Petrella, J. R., Doraiswamy, P. M., & Alzheimer’s Disease Neuroimaging Initiative, . (2013). Prevalence of Alzheimer's pathologic endophenotypes in asymptomatic and mildly impaired first-degree relatives. PLoS One, 8(4), e60747. https://doi.org/10.1371/journal.pone.0060747
Lampert, Erika J., Kingshuk Roy Choudhury, Christopher A. Hostage, Jeffrey R. Petrella, P Murali Doraiswamy, and P Murali Alzheimer’s Disease Neuroimaging Initiative. “Prevalence of Alzheimer's pathologic endophenotypes in asymptomatic and mildly impaired first-degree relatives.PLoS One 8, no. 4 (2013): e60747. https://doi.org/10.1371/journal.pone.0060747.
Lampert EJ, Roy Choudhury K, Hostage CA, Petrella JR, Doraiswamy PM, Alzheimer’s Disease Neuroimaging Initiative. Prevalence of Alzheimer's pathologic endophenotypes in asymptomatic and mildly impaired first-degree relatives. PLoS One. 2013;8(4):e60747.
Lampert, Erika J., et al. “Prevalence of Alzheimer's pathologic endophenotypes in asymptomatic and mildly impaired first-degree relatives.PLoS One, vol. 8, no. 4, 2013, p. e60747. Pubmed, doi:10.1371/journal.pone.0060747.
Lampert EJ, Roy Choudhury K, Hostage CA, Petrella JR, Doraiswamy PM, Alzheimer’s Disease Neuroimaging Initiative. Prevalence of Alzheimer's pathologic endophenotypes in asymptomatic and mildly impaired first-degree relatives. PLoS One. 2013;8(4):e60747.

Published In

PLoS One

DOI

EISSN

1932-6203

Publication Date

2013

Volume

8

Issue

4

Start / End Page

e60747

Location

United States

Related Subject Headings

  • tau Proteins
  • ROC Curve
  • Prevalence
  • Organ Size
  • Middle Aged
  • Humans
  • Hippocampus
  • General Science & Technology
  • Family
  • Endophenotypes