CDK5RAP2 gene and tau pathophysiology in late-onset sporadic Alzheimer's disease

Alzheimers Dement. 2018 Jun;14(6):787-796. doi: 10.1016/j.jalz.2017.12.004. Epub 2018 Jan 19.


Introduction: Because currently known Alzheimer's disease (AD) single-nucleotide polymorphisms only account for a small fraction of the genetic variance in this disease, there is a need to identify new variants associated with AD.

Methods: Our team performed a genome-wide association study in the Quebec Founder Population isolate to identify novel protective or risk genetic factors for late-onset sporadic AD and examined the impact of these variants on gene expression and AD pathology.

Results: The rs10984186 variant is associated with an increased risk of developing AD and with a higher CDK5RAP2 mRNA prevalence in the hippocampus. On the other hand, the rs4837766 variant, which is among the best cis-expression quantitative trait loci in the CDK5RAP2 gene, is associated with lower mild cognitive impairment/AD risk and conversion rate.

Discussion: The rs10984186 risk and rs4837766 protective polymorphic variants of the CDK5RAP2 gene might act as potent genetic modifiers for AD risk and/or conversion by modulating the expression of this gene.

Keywords: Alzheimer's disease; CDK5RAP2; Genetics; Neurofibrillary tangles; Tau.

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
  • Alzheimer Disease / genetics*
  • Alzheimer Disease / pathology
  • Cell Cycle Proteins
  • Cognitive Dysfunction / genetics
  • Female
  • Genetic Predisposition to Disease
  • Genome-Wide Association Study
  • Hippocampus / pathology
  • Humans
  • Intracellular Signaling Peptides and Proteins / genetics*
  • Intracellular Signaling Peptides and Proteins / metabolism
  • Male
  • Nerve Tissue Proteins / genetics*
  • Nerve Tissue Proteins / metabolism
  • Polymorphism, Single Nucleotide
  • Quantitative Trait Loci
  • tau Proteins / metabolism*


  • CDK5RAP2 protein, human
  • Cell Cycle Proteins
  • Intracellular Signaling Peptides and Proteins
  • Nerve Tissue Proteins
  • tau Proteins