Recent insights into the molecular genetics of dementia

Trends Neurosci. 2009 Aug;32(8):451-61. doi: 10.1016/j.tins.2009.05.005. Epub 2009 Jul 27.

Abstract

Our understanding of the molecular genetic basis of two common neurodegenerative dementias, Alzheimer's disease (AD) and frontotemporal lobar degeneration (FTLD), has greatly advanced in recent years. Progranulin mutations were identified as a major cause of FTLD and a potential susceptibility factor for other forms of dementia. In addition, through copy-number analyses of previously identified disease genes and the study of microRNA regulation in dementia, new evidence emerged to support the view that subtle variability in the expression of known disease proteins could increase the risk for sporadic forms of dementia. Finally, in late-onset AD populations, the first genome-wide association studies were performed and novel potential AD susceptibility genes reported. These exciting findings provide novel insights into the disease mechanisms underlying dementia and hold promise for the development of potential treatments.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • DNA-Binding Proteins / genetics
  • DNA-Binding Proteins / metabolism
  • Dementia / classification
  • Dementia / genetics*
  • Dementia / metabolism
  • Gene Dosage / physiology
  • Gene Expression Regulation / genetics
  • Genetic Predisposition to Disease*
  • Genetic Variation / genetics*
  • Humans
  • Intercellular Signaling Peptides and Proteins / genetics
  • Intercellular Signaling Peptides and Proteins / metabolism
  • Progranulins
  • RNA, Messenger / metabolism

Substances

  • DNA-Binding Proteins
  • GRN protein, human
  • Intercellular Signaling Peptides and Proteins
  • Progranulins
  • RNA, Messenger