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Title: APOE effect on Alzheimer's disease biomarkers in older adults with significant memory concern

This study assessed apolipoprotein E (APOE) ε4 carrier status effects on Alzheimer's disease imaging and cerebrospinal fluid (CSF) biomarkers in cognitively normal older adults with significant memory concerns (SMC). Cognitively normal, SMC, and early mild cognitive impairment participants from Alzheimer's Disease Neuroimaging Initiative were divided by APOE ε4 carrier status. Diagnostic and APOE effects were evaluated with emphasis on SMC. Additional analyses in SMC evaluated the effect of the interaction between APOE and [ 18F]Florbetapir amyloid positivity on CSF biomarkers. SMC ε4+ showed greater amyloid deposition than SMC ε4-, but no hypometabolism or medial temporal lobe (MTL) atrophy. SMC ε4+ showed lower amyloid beta 1-42 and higher tau/p-tau than ε4-, which was most abnormal in APOE ε4+ and cerebral amyloid positive SMC. Lastly, SMC APOE ε4+ show abnormal changes in amyloid and tau biomarkers, but no hypometabolism or MTL neurodegeneration, reflecting the at-risk nature of the SMC group and the importance of APOE in mediating this risk.
Authors:
 [1] ;  [2] ;  [2] ;  [3] ;  [2] ;  [4] ;  [5] ;  [6] ;  [7] ;  [8] ;  [9] ;  [10] ;  [10] ;  [11] ;  [12]
  1. Indiana Univ., Indianapolis, IN (United States). School of Medicine, Dept. of Radiology and Imaging Sciences, Center for Neuroimaging; Indiana Univ., Indianapolis, IN (United States). School of Medicine, Indiana Alzheimer Disease Center
  2. Indiana Univ., Indianapolis, IN (United States). School of Medicine, Dept. of Radiology and Imaging Sciences, Center for Neuroimaging; Indiana Univ., Indianapolis, IN (United States). School of Medicine, Indiana Alzheimer Disease Center; Indiana Univ., Indianapolis, IN (United States). School of Medicine, Center for Computational Biology and Bioinformatics
  3. Indiana Univ., Indianapolis, IN (United States). School of Medicine, Indiana Alzheimer Disease Center; Indiana Univ., Indianapolis, IN (United States). School of Medicine, Dept. of Medical and Molecular Genetics
  4. Mayo Clinic, Rochester, MN (United States). Dept. of Neurology
  5. Mayo Clinic, Rochester, MN (United States). Dept. of Radiology
  6. Univ. of California, Davis, CA (United States). Dept. of Public Health Sciences, Division of Biostatistics
  7. Univ. of California, San Diego, CA (United States). Dept. of Neurology
  8. Univ. of Michigan, Ann Arbor, MI (United States). Dept. of Radiology
  9. Univ. of California, Berkeley, CA (United States). Dept. of Neurology
  10. Univ. of Pennsylvania, Philadelphia, PA (United States). School of Medicine, Dept. of Pathology and Lab. Medicine
  11. Univ. of California, San Francisco, CA (United States). Dept. of Radiology, Medicine and Psychiatry; Dept. of Veterans Affairs Medical Center, San Francisco, CA (United States)
  12. Indiana Univ., Indianapolis, IN (United States). School of Medicine, Dept. of Radiology and Imaging Sciences, Center for Neuroimaging; Indiana Univ., Indianapolis, IN (United States). School of Medicine, Indiana Alzheimer Disease Center; Indiana Univ., Indianapolis, IN (United States). School of Medicine, Center for Computational Biology and Bioinformatics; Indiana Univ., Indianapolis, IN (United States). School of Medicine, Dept. of Medical and Molecular Genetics
Publication Date:
Grant/Contract Number:
AC02-05CH11231; U01 AG024904; W81XWH-12-2-0012; P30 AG010129; K01 AG030514
Type:
Accepted Manuscript
Journal Name:
Alzheimer's & Dementia
Additional Journal Information:
Journal Volume: 11; Journal Issue: 12; Journal ID: ISSN 1552-5260
Publisher:
Elsevier
Research Org:
Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States)
Sponsoring Org:
USDOE; National Institutes of Health (NIH)
Country of Publication:
United States
Language:
English
Subject:
60 APPLIED LIFE SCIENCES; Significant memory concern; SMC; Subjective cognitive decline; SCD; Apolipoprotein E; APOE; Neuroimaging; [18F]Florbetapir PET; [18F]Fluorodeoxyglucose; FDG; PET; Structural magnetic resonance imaging (MRI); Cerebrospinal fluid; CSF; Alzheimer's Disease Neuroimaging Initiative; ADNI
OSTI Identifier:
1378678