Correlations Between Single Nucleotide Polymorphisms, Cognitive Dysfunction, and Postmortem Brain Pathology in Alzheimer's Disease Among Han Chinese

Neurosci Bull. 2019 Apr;35(2):193-204. doi: 10.1007/s12264-019-00343-2. Epub 2019 Feb 19.

Abstract

In this study, the distribution of five Alzheimer's disease (AD)-related single nucleotide polymorphisms (SNPs) in the Han population was examined in combination with the evaluation of clinical cognition and brain pathological analysis. The associations among SNPs, clinical daily cognitive states, and postmortem neuropathological changes were analyzed in 110 human brains from the Chinese Academy of Medical Sciences/Peking Union Medical College (CAMS/PUMC) Human Brain Bank. APOE ε4 (OR = 4.482, P = 0.004), the RS2305421 GG genotype (adjusted OR = 4.397, P = 0.015), and the RS10498633 GT genotype (adjusted OR = 2.375, P = 0.028) were associated with a higher score on the ABC (Aβ plaque score, Braak NFT stage, and CERAD neuritic plaque score) dementia scale. These results advance our understanding of the pathogenesis of AD, the relationship between pathological diagnosis and clinical diagnosis, and the SNPs in the Han population for future research.

Keywords: ADAM10; APOE ε4; Alzheimer’s disease; Human brain bank; SLC24A4.

MeSH terms

  • ADAM10 Protein / genetics
  • Adult
  • Aged
  • Aged, 80 and over
  • Alzheimer Disease / genetics*
  • Alzheimer Disease / pathology*
  • Amyloid Precursor Protein Secretases / genetics
  • Antiporters / genetics
  • Apolipoprotein E4 / genetics
  • Asian People / genetics
  • Brain / pathology*
  • Cognitive Dysfunction / genetics*
  • Cognitive Dysfunction / pathology*
  • Female
  • Genetic Predisposition to Disease
  • Humans
  • Male
  • Membrane Proteins / genetics
  • Middle Aged
  • Polymorphism, Single Nucleotide*

Substances

  • Antiporters
  • Apolipoprotein E4
  • Membrane Proteins
  • SLC24A4 protein, human
  • Amyloid Precursor Protein Secretases
  • ADAM10 Protein
  • ADAM10 protein, human