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Title: Alzheimer risk genes modulate the relationship between plasma apoE and cortical PiB binding

Objective: We investigated the association between apoE protein plasma levels and brain amyloidosis and the effect of the top 10 Alzheimer disease (AD) risk genes on this association. Methods: Our dataset consisted of 18 AD, 52 mild cognitive impairment, and 3 cognitively normal Alzheimer's Disease Neuroimaging Initiative 1 (ADNI1) participants with available [ 11C]-Pittsburgh compound B (PiB) and peripheral blood protein data. We used cortical pattern matching to study associations between plasma apoE and cortical PiB binding and the effect of carrier status for the top 10 AD risk genes. Results: Low plasma apoE was significantly associated with high PiB SUVR, except in the sensorimotor and entorhinal cortex. For BIN1 rs744373, the association was observed only in minor allele carriers. For CD2AP rs9349407 and CR1 rs3818361, the association was preserved only in minor allele noncarriers. We did not find evidence for modulation by CLU, PICALM, ABCA7, BIN1, and MS4A6A. Conclusions: Our data show that BIN1 rs744373, CD2AP rs9349407, and CR1 rs3818361 genotypes modulate the association between apoE protein plasma levels and brain amyloidosis, implying a potential epigenetic/downstream interaction.
Authors:
 [1] ;  [2] ;  [3] ;  [4] ;  [5] ;  [3] ;  [6] ;  [7] ;  [6] ;  [8] ;  [9] ;  [9] ;  [10] ;  [11] ;  [12]
  1. Univ. of California, Berkeley, CA (United States)
  2. Oakland Univ. William Beaumont School of Medicine, Rochester, MI (United States); Univ. of California, Los Angeles, CA (United States). David Geffen School of Medicine. Dept. of Neurology
  3. Univ. of California, Los Angeles, CA (United States). David Geffen School of Medicine. Dept. of Neurology
  4. Drexel Univ., Philadelphia, PA (United States). College of Medicine
  5. Northwestern Univ., Chicago, IL (United States). Feinberg School of Medicine
  6. Univ. of California, Los Angeles, CA (United States). David Geffen School of Medicine. Dept. of Neurology; Veterans Affairs Greater Los Angeles Healthcare System, Los Angeles, CA (United States)
  7. Univ. of California, Los Angeles, CA (United States). School of Nursing
  8. Indiana Univ., Indianapolis, IN (United States). Dept. of Radiology and Imaging Sciences. Center for Neuroimaging. School of Medicine
  9. Univ. of Pennsylvania, Philadelphia, PA (United States). School of Medicine. Dept. of Pathology and Laboratory Medicine
  10. Univ. of California, Berkeley, CA (United States). Dept. of Public Health and Neuroscience
  11. Dept. of Veterans' Affairs Medical Center, San Francisco, CA (United States)
  12. Univ. of California, Los Angeles, CA (United States). David Geffen School of Medicine. Dept. of Neurology; Indiana Univ., Indianapolis, IN (United States). Dept. of Radiology and Imaging Sciences. Center for Neuroimaging. Dept. of Neurology. Dept. of Medical and Molecular Genetics. School of Medicine
Publication Date:
Grant/Contract Number:
AC02-05CH11231; U01 AG024904; NIA R01 AG040770; NIA K02 AG048240; NIA P50 AG16570; W81XWH-12-2-0012
Type:
Accepted Manuscript
Journal Name:
Neurology Genetics
Additional Journal Information:
Journal Volume: 1; Journal Issue: 3; Journal ID: ISSN 2376-7839
Research Org:
Indiana Univ., Indianapolis, IN (United States); Univ. of California, Los Angeles, CA (United States); Univ. of California, Berkeley, CA (United States)
Sponsoring Org:
USDOE; National Inst. of Health (NIH) (United States); USDOD
Contributing Orgs:
Oakland Univ. William Beaumont School of Medicine, Rochester, MI (United States); Drexel Univ., Philadelphia, PA (United States); Northwestern Univ., Chicago, IL (United States); Veterans Affairs Greater Los Angeles Healthcare System, Los Angeles, CA (United States); Univ. of Pennsylvania, Philadelphia, PA (United States); Dept. of Veterans' Affairs Medical Center, San Francisco, CA (United States)
Country of Publication:
United States
Language:
English
Subject:
60 APPLIED LIFE SCIENCES; 59 BASIC BIOLOGICAL SCIENCES
OSTI Identifier:
1378592