Alzheimer’s disease and histone code alterations

Abstract

Substantial progress has been made in identifying Alzheimer’s disease (AD) risk-associated variants using genome-wide association studies (GWAS). The majority of these risk variants reside in noncoding regions of the genome making their functional evaluation difficult; however, they also infer the presence of unconventional regulatory regions that may reside at these locations. We know from these studies that rare familial cases of AD account for less than 5% of all AD cases and autosomal dominant mutations in APP, PSEN1 and PSEN2 account for less than 10% of the genetic basis of these familial cases [1]. The sporadic form of AD, while more complex, still has a substantial genetic component evidenced by observational studies where 30–48% of AD patients have a first degree relative who is also affected [2]. In addition, the strongest risk factor after age is the APOE E4 polymorphism, and more than 20 other risk variants have been identified to date, reviewed in two recent papers [3, 4]. Monozygotic twin studies have revealed a discordance for AD, implicating that a combination of epigenetic and genetic factors are likely involved in the development of AD [5].