Association of cerebrospinal fluid Aβ42 with A2M gene in cognitively normal subjects

Steven P. Millard, Franziska Lutz, Ge Li, Douglas R. Galasko, Martin R. Farlow, Joseph Quinn, Jeffrey Kaye, James B. Leverenz, Debby Tsuang, Chang En Yu, Elaine R. Peskind, Lynn M. Bekris

Research output: Contribution to journalArticle

3 Scopus citations

Abstract

Low cerebrospinal fluid (CSF) Aβ42 levels correlate with increased brain Aβ deposition in Alzheimer's disease (AD), which suggests a disruption in the degradation and clearance of Aβ from the brain. In addition, APOE ε4 carriers have lower CSF Aβ42 levels than non-carriers. The hypothesis of this investigation was that CSF Aβ42 levels would correlate with regulatory region variation in genes that are biologically associated with degradation or clearance of Aβ from the brain. CSF Aβ42 levels were tested for associations with Aβ degradation and clearance genes and APOE ε4. Twenty-four SNPs located within the 5' and 3' regions of 12 genes were analyzed. The study sample consisted of 99 AD patients and 168 cognitively normal control subjects. CSF Aβ42 levels were associated with APOE ε4 status in controls but not in AD patients; A2M regulatory region SNPs were also associated with CSF Aβ42 levels in controls butnot in AD patients, even after adjusting for APOE ε4. These results suggest that genetic variation within the A2M gene influences CSF Aβ42 levels.

Original languageEnglish (US)
Pages (from-to)357-364
Number of pages8
JournalNeurobiology of Aging
Volume35
Issue number2
DOIs
StatePublished - Feb 2014

    Fingerprint

Keywords

  • A2M
  • Alpha-2-Macroglobulin
  • Alzheimer's disease
  • APOE
  • Cerebrospinal fluid

ASJC Scopus subject areas

  • Clinical Neurology
  • Neuroscience(all)
  • Aging
  • Developmental Biology
  • Geriatrics and Gerontology

Cite this

Millard, S. P., Lutz, F., Li, G., Galasko, D. R., Farlow, M. R., Quinn, J., Kaye, J., Leverenz, J. B., Tsuang, D., Yu, C. E., Peskind, E. R., & Bekris, L. M. (2014). Association of cerebrospinal fluid Aβ42 with A2M gene in cognitively normal subjects. Neurobiology of Aging, 35(2), 357-364. https://doi.org/10.1016/j.neurobiolaging.2013.07.027