Absence of coding somatic single nucleotide variants within well-known candidate genes in late-onset sporadic Alzheimer's Disease based on the analysis of multi-omics data

Neurobiol Aging. 2021 Dec;108:207-209. doi: 10.1016/j.neurobiolaging.2021.07.010. Epub 2021 Jul 21.


Somatic mutations arise randomly or are induced by environmental factors, which may increase the risk of Alzheimer's disease (AD). Identifying somatic mutations in sporadic AD (SAD) may provide new insight of the disease. To evaluate the potential contribution of somatic single nucleotide variations (SNVs), particularly that of well-known AD-candidate genes, we investigated sequencing data sets from four platforms: whole-genome sequencing (WGS), deep whole-exome sequencing (WES) on paired brain and liver samples, RNA sequencing (RNA-seq), and single-cell whole-genome sequencing (scWGS) of brain samples from 16 AD patients and 16 non-AD individuals. We found that the average number, mean variant allele fractions (VAFs) and mutational signatures of somatic SNVs have similar distributions between AD brains and non-AD brains. We did not identify any somatic SNVs within coding regions of the APP, PSEN1, PSEN2, nor in APOE. This study shows that somatic SNVs within the coding region of AD-candidate genes are unlikely to be a common causal factor for SAD.

Keywords: Alzheimer's disease; Candidate genes; Multiple sequencing datasets; Somatic SNVs.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alzheimer Disease / genetics*
  • Amyloid beta-Protein Precursor / genetics
  • Apolipoproteins E / genetics
  • Datasets as Topic
  • Female
  • Genetic Association Studies / methods*
  • Humans
  • Male
  • Polymorphism, Single Nucleotide / genetics*
  • Presenilin-1 / genetics
  • Presenilin-2 / genetics
  • Whole Genome Sequencing / methods


  • APP protein, human
  • Amyloid beta-Protein Precursor
  • Apolipoproteins E
  • PSEN1 protein, human
  • PSEN2 protein, human
  • Presenilin-1
  • Presenilin-2