Molecular genetics and biology of dementia

Abstract

Dementia is caused by an interplay between genes and lifestyle and environmental factors. Recent advances in genetic and molecular biology have provided valuable insights into the pathogenesis of underlying dementia for not only in those with clear genetic aetiology, but also in those with no familial basis. The advent of large-scale genome-wide association studies (GWAS) and the more recent next-generation sequencing has unravelled some great insight into the possible underlying mechanisms involved in neurodegenerative disorders such as Alzheimer’s disease, vascular dementia, frontotemporal lobar degeneration, and Lewy body disease. Interestingly, there is a common theme and these studies have outlined several pathways such as immune regulation, lipid metabolism, protein folding, and protein transport. This brings hope for future treatment strategies and therapeutic targets. Finally, most dementias are multifactorial and not only caused by genetic factors. Therefore, more research is needed, particularly investigations of epistasis and gene-by-environment interaction.