Genetic factors associated with the predisposition to late onset Alzheimer's disease

Gene. 2019 Jul 30;707:212-215. doi: 10.1016/j.gene.2019.05.030. Epub 2019 May 15.

Abstract

Background: Alzheimer's disease is a progressive, irreversible neurodegenerative disorder characterized by loss of memory and cognitive skills. More than 90% of cases are sporadic and have later age of onset. Many studies have shown a genetic predisposition for late onset Alzheimer's disease (LOAD). The most studied genetic predisposition factor is apolipoprotein E gene besides other susceptibility genes involved in vascular pathologies, homocysteine metabolism, and neuronal growth and differentiation such as methylenetetrahydrofolate reductase (MTHFR), angiotensin-converting enzyme (ACE), APOB and brain derived neurotrophic factor (BDNF).

Methods: In this study Factor V Leiden (G1691A) and H1299R, prothrombin G20210A, Factor XIII V34L, B-fibrinogen -455G>A, PAI-1 5G/4G, HPA1 b/a, MTHFR C677T, MTHFR A1298C, APOE, ACE I/D, BDNF C270T and G196A polymorphisms were evaluated in 100 LOAD patients and 100 age matched healthy controls.

Results: APOE4 allele, MTHFR CCA1298C and BDNF TTC270T genotypes were significantly higher in LOAD patients compared to the control group (p < 0.001, p = 0.04, p = 0.03, respectively). There were no significant associations between other genotypes and allele frequencies. Mini-Mental State Examination (MMSE) scores and age at onset of the patients were also evaluated for each and combined genotypes. Age at onset was significantly lowered by about approximately 4 and 5 years in patients carrying BDNF TTC270T and MTHFR TTC677T genotypes, respectively.

Conclusion: APOE, MTHFR A1298C and BDNF C270T polymorphisms may be associated with LOAD and BDNF and MTHFR alleles may play a role in the age at onset of the LOAD.

Keywords: ACE; BDNF; Genetic polymorphism; Late-onset Alzheimer's disease; MTHFR.

MeSH terms

  • Age of Onset
  • Aged
  • Aged, 80 and over
  • Alzheimer Disease / genetics*
  • Apolipoproteins E / genetics*
  • Brain-Derived Neurotrophic Factor / genetics*
  • Case-Control Studies
  • Female
  • Gene Frequency
  • Genetic Association Studies
  • Genetic Predisposition to Disease
  • Genetic Variation
  • Genotype
  • Humans
  • Male
  • Methylenetetrahydrofolate Reductase (NADPH2) / genetics*
  • Middle Aged
  • Mutation*

Substances

  • ApoE protein, human
  • Apolipoproteins E
  • Brain-Derived Neurotrophic Factor
  • BDNF protein, human
  • MTHFR protein, human
  • Methylenetetrahydrofolate Reductase (NADPH2)