Is the presenilin-1 E318G missense mutation a risk factor for Alzheimer's disease?

Neurosci Lett. 2000 Jan 7;278(1-2):65-8. doi: 10.1016/s0304-3940(99)00891-5.

Abstract

Nearly all of the presenilin-1 (PSEN-1) mutations are missense mutations leading to Alzheimer's disease (AD). The role of the mutation E318G (a substitution of glutamic acid to glycine) in the PSEN-1 is controversial. It has been found both in AD patients and in non-demented control individuals. Using the polymerase chain reaction and the restriction fragment length polymorphism method, we screened for E318G mutation in a total of 16 familial (FAD) cases, in 64 sporadic neuropathologically confirmed AD cases and in 270 non-demented controls including 35 neuropathologically confirmed individuals. We detected the E318G mutation in four FAD cases, seven sporadic AD cases and 10 control individuals with highly varying onset-ages. Odds ratios for carrying the mutation were 7.6 and 3 in FAD and sporadic AD cases, respectively. Our results suggest that this mutation could be a risk factor in the Finnish FAD and sporadic AD population. It may be in linkage disequilibrium with a pathogenic change somewhere else in the PSEN-1 gene or in close proximity to the PSEN-1 gene.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Alzheimer Disease / epidemiology
  • Alzheimer Disease / genetics*
  • Amino Acid Substitution*
  • Apolipoprotein E4
  • Apolipoproteins E / genetics
  • Female
  • Finland / epidemiology
  • Gene Frequency
  • Genetic Predisposition to Disease
  • Genotype
  • Humans
  • Linkage Disequilibrium
  • Male
  • Membrane Proteins / genetics*
  • Middle Aged
  • Odds Ratio
  • Point Mutation*
  • Presenilin-1
  • Risk Factors

Substances

  • Apolipoprotein E4
  • Apolipoproteins E
  • Membrane Proteins
  • PSEN1 protein, human
  • Presenilin-1