Toward an integrated genetic and epigenetic approach to Alzheimer's disease.

Epigenetics is the study of mitotically heritable, but reversible, changes in gene expression brought about principally through alterations in DNA methylation and chromatin structure. The comprehensive review by Mastroeni et al. (Mastroeni, D., Grover, A., Delvaux, E., Whiteside, C., Coleman, P., Rogers, J., 2010. Epigenetic mechanisms in Alzheimer's disease. Neurobiol. Aging, doi:10.1016/j.neurobiolaging.2010.08.017) in this issue describes mounting evidence for an involvement of epigenetic alterations in the etiology of Alzheimer's disease (AD), highlighting the potential of epigenomic approaches for uncovering novel molecular pathways involved in pathology. Here, we briefly describe some methodological issues related to epigenomic studies using postmortem brain tissue in Alzheimer's disease, and argue for an integrated genetic-epigenetic approach to disease etiology.