Using induced pluripotent stem cells to explore genetic and epigenetic variation associated with Alzheimer's disease

• Published in: Epigenomics Vol. 9; no. 11; pp. 1455 - 1468
• Main Authors: Imm, Jennifer, Kerrigan, Talitha L, Jeffries, Aaron, Lunnon, Katie
• Format: Journal Article
• Language: English
• Published: England Future Medicine Ltd 01.11.2017
• Subjects: Age; Alzheimer Disease - genetics; Alzheimer Disease - pathology; Alzheimer's disease; Cell adhesion & migration; CRISPR-Cas9; Dementia; Deoxyribonucleic acid; DNA; DNA methylation; Editing; Epigenesis, Genetic; Epigenetics; Gene expression; Genetic diversity; Genetic Variation; Genome editing; Genomes; Humans; Induced Pluripotent Stem Cells - cytology; Induced Pluripotent Stem Cells - metabolism; Neurodegenerative diseases; Neurons; Pathology; Pluripotency; Proteins; Quantitative genetics; Stem cells; DNA methylation; Alzheimer's disease; CRISPR-Cas9
• ISSN: 1750-1911; 1750-192X
• DOI: 10.2217/epi-2017-0076

It is thought that both genetic and epigenetic variation play a role in Alzheimer's disease initiation and progression. With the advent of somatic cell reprogramming into induced pluripotent stem cells it is now possible to generate patient-derived cells that are able to more accurately model and recapitulate disease. Furthermore, by combining this with recent advances in (epi)genome editing technologies, it is possible to begin to examine the functional consequence of previously nominated genetic variants and infer epigenetic causality from recently identified epigenetic variants. In this review, we explore the role of genetic and epigenetic variation in Alzheimer's disease and how the functional relevance of nominated loci can be investigated using induced pluripotent stem cells and (epi)genome editing techniques.