Applying gene-editing technology to elucidate the functional consequence of genetic and epigenetic variation in Alzheimer's disease

Brain Pathol. 2020 Sep;30(5):992-1004. doi: 10.1111/bpa.12881.

Abstract

Recent studies have highlighted a potential role of genetic and epigenetic variation in the development of Alzheimer's disease. Application of the CRISPR-Cas genome-editing platform has enabled investigation of the functional impact that Alzheimer's disease-associated gene mutations have on gene expression. Moreover, recent advances in the technology have led to the generation of CRISPR-Cas-based tools that allow for high-throughput interrogation of different risk variants to elucidate the interplay between genomic regulatory features, epigenetic modifications, and chromatin structure. In this review, we examine the various iterations of the CRISPR-Cas system and their potential application for exploring the complex interactions and disruptions in gene regulatory circuits that contribute to Alzheimer's disease.

Keywords: Alzheimer's disease (AD); CRISPR; epigenetics; genetics; genome editing.

MeSH terms

  • Alzheimer Disease / genetics*
  • Alzheimer Disease / metabolism
  • Alzheimer Disease / pathology*
  • CRISPR-Cas Systems / genetics
  • Clustered Regularly Interspaced Short Palindromic Repeats / genetics
  • Cognitive Dysfunction
  • Epigenesis, Genetic / genetics
  • Epigenomics / methods
  • Gene Editing / methods*
  • Genetic Predisposition to Disease / genetics
  • Genomics / methods
  • Humans
  • Mutation / genetics
  • Neurodegenerative Diseases / genetics
  • Technology