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

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.