Using Induced Pluripotent Stem Cells to Explore Genetic and Epigenetic Variation Associated With Alzheimer’S Disease

Abstract

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.

Keywords::

• Alzheimer’s disease
• CRISPR-Cas9
• DNA methylation

Financial & competing interests disclosure

This work was funded by an Alzheimer’s Society project grant to K Lunnon (grant number AS-PG-14-038), an Alzheimer’s Research UK network cooperation grant to K Lunnon (grant number ARUK-NCG2017A-5) and an Alzheimer’s Association new investigator research grant to K Lunnon (grant number NIRG-14-320878). J Imm is supported by the Alzheimer’s Society Doctoral Training Centre in Dementia Research at the University of Exeter (grant number AS-DTC-2014-030) and the Garfield Weston Foundation. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.

Additional information

Funding

This work was funded by an Alzheimer’s Society project grant to K Lunnon (grant number AS-PG-14-038), an Alzheimer’s Research UK network cooperation grant to K Lunnon (grant number ARUK-NCG2017A-5) and an Alzheimer’s Association new investigator research grant to K Lunnon (grant number NIRG-14-320878). J Imm is supported by the Alzheimer’s Society Doctoral Training Centre in Dementia Research at the University of Exeter (grant number AS-DTC-2014-030) and the Garfield Weston Foundation. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed. No writing assistance was utilized in the production of this manuscript.