A potential endophenotype for Alzheimer's disease: cerebrospinal fluid clusterin

Neurobiol Aging. 2016 Jan;37:208.e1-208.e9. doi: 10.1016/j.neurobiolaging.2015.09.009. Epub 2015 Sep 25.

Abstract

Genome-wide association studies have associated clusterin (CLU) variants with Alzheimer's disease (AD). However, the role of CLU on AD pathogenesis is not totally understood. We used cerebrospinal fluid (CSF) and plasma CLU levels as endophenotypes for genetic studies to understand the role of CLU in AD. CSF, but not plasma, CLU levels were significantly associated with AD status and CSF tau/amyloid-beta ratio, and highly correlated with CSF apolipoprotein E (APOE) levels. Several loci showed almost genome-wide significant associations including LINC00917 (p = 3.98 × 10(-7)) and interleukin 6 (IL6, p = 9.94 × 10(-6), in the entire data set and in the APOE ε4- individuals p = 7.40 × 10(-8)). Gene ontology analyses suggest that CSF CLU levels may be associated with wound healing and immune response which supports previous functional studies that demonstrated an association between CLU and IL6. CLU may play a role in AD by influencing immune system changes that have been observed in AD or by disrupting healing after neurodegeneration.

Keywords: APOE; Alzheimer's disease; Cerebrospinal fluid; Clusterin; Gene ontology; Immune response.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Aged
  • Aged, 80 and over
  • Alzheimer Disease / cerebrospinal fluid*
  • Alzheimer Disease / genetics*
  • Alzheimer Disease / immunology
  • Alzheimer Disease / physiopathology
  • Apolipoprotein E4
  • Apolipoproteins E / cerebrospinal fluid
  • Biomarkers / cerebrospinal fluid
  • Clusterin / blood
  • Clusterin / cerebrospinal fluid*
  • Clusterin / physiology
  • Endophenotypes*
  • Female
  • Gene Ontology
  • Genome-Wide Association Study*
  • Humans
  • Immunity / genetics
  • Male
  • Nerve Degeneration / genetics
  • Wound Healing / genetics

Substances

  • Apolipoprotein E4
  • Apolipoproteins E
  • Biomarkers
  • Clusterin