Case-control analysis of leucine-rich repeat kinase 2 protective variants in Alzheimer's disease

Neurobiol Aging. 2018 Apr:64:157.e7-157.e9. doi: 10.1016/j.neurobiolaging.2017.11.012. Epub 2017 Nov 27.

Abstract

Amyloid is the main pathological substrate of Alzheimer's disease (AD) and has been described in leucine-rich repeat kinase 2 (LRRK2) carriers with Parkinson's disease. LRRK2 has been linked with amyloid precursor protein pathways in neurodegeneration. Two common LRRK2 variants, R1398H and N551K, have been shown to be protective in multiple Parkinson's disease cohorts. We hypothesized that R1398H and N551K may be protective in AD. In a case-control study involving 1390 subjects (719 controls and 671 AD cases), R1398H was demonstrated in 16.8% of AD cases compared to 16.7% in controls (odds ratio = 1.01, 95% confidence interval = 0.76-1.34, p = 0.94), whereas N551K was demonstrated in 17.3% of AD cases compared to 17.2% of controls (odds ratio = 1.00, 95% confidence interval = 0.76-1.32, p = 0.98). Overall, these results suggest that LRRK2 R1398H or N551K variants do not appear to modulate the risk of AD.

Keywords: Alzheimer's disease; Genes; LRRK2; Variants.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Alzheimer Disease / etiology
  • Alzheimer Disease / genetics*
  • Alzheimer Disease / pathology
  • Alzheimer Disease / prevention & control
  • Amyloid beta-Protein Precursor / metabolism
  • Case-Control Studies
  • Female
  • Genetic Association Studies*
  • Genetic Variation*
  • Humans
  • Leucine-Rich Repeat Serine-Threonine Protein Kinase-2 / genetics*
  • Male
  • Middle Aged
  • Nerve Degeneration / genetics
  • Neuroprotection / genetics
  • Risk
  • Signal Transduction / genetics

Substances

  • Amyloid beta-Protein Precursor
  • LRRK2 protein, human
  • Leucine-Rich Repeat Serine-Threonine Protein Kinase-2