Genetic and Epigenetic Architecture of Alzheimer’s Dementia

• Published in: Current genetic medicine reports Vol. 4; no. 1; pp. 7 - 15
• Main Authors: Cervera-Carles, Laura, Clarimón, Jordi
• Format: Journal Article
• Language: English
• Published: New York Springer US 01.03.2016
• Subjects: Internal Medicine; Medicine; Medicine & Public Health; Neurogenetics and Psychiatric Genetics; Neurogenetics/Psychiatric Genetics (M Hiltunen and D Marenda; Section Editors; Genetic risk variants; Mendelian genes; Epigenetic marks; Alzheimer’s disease
• ISSN: 2167-4876; 2167-4876
• DOI: 10.1007/s40142-016-0086-1

Alzheimer’s disease (AD) is the most common neurodegenerative disease, affecting up to 5 % of the population over 65 years old. It is characterized by the accumulation of amyloid-β peptide and aggregation of hyperphosphorylated tau protein. Mutations in pivotal genes ( APP , PSEN1, and PSEN2 ) result in the autosomal dominant form of the disease; however, the genetic cause of the majority of cases remains unexplained. Advances in genomic techniques have allowed the discovery of common variants that influence susceptibility to AD. In addition, low-frequency and rare variants in a small number of genes have emerged as important contributors of disease risk. Recent studies have focused on the epigenetic changes in affected individuals, such as DNA methylation patterns or microRNA levels, highlighting the possible involvement of these mechanisms in the etiology of AD. Here we review the known genetic and epigenetic factors underlying AD, emphasizing the molecular networks that appear to be fundamental players in its etiology.