Genetics of Dementia

Michael Bjørn Russell, University of Oslo, Nordbyhagen, Oslo, Norway

Published online: July 2012

DOI: 10.1002/9780470015902.a0023871

Dementia is a syndrome and not a single disease. It is caused by a primary brain disorders or a neurological/somatic disorders with brain involvement. Alzheimer disease is the most common dementia. Approximately 1% have early‐onset Alzheimer disease, often caused by mutation in the APP, PSEN1 or PSEN2 gene. Late‐onset Alzheimer disease has a complex inheritance. The APOE ɛ4 allele is a major risk factor for late‐onset Alzheimer disease, while the ɛ2 allele has a protective effect. Genome‐wide association studies indicate that BIN1, CRI, CLU and PICALM play a role in late‐onset Alzheimer disease, while other potential genes requires further investigation. Stroke is a syndrome and not a single disease. CADASIL is the most common autosomal dominant inherited cause of stroke and vascular dementia caused by mutations in the NOTCH3 gene. It is the stroke itself rather than the underlying vascular risk factors that cause the dementia.

Key Concepts:

  • Dementia is a syndrome and not a single disease.
  • Alzheimer disease is the most common primary brain disorders causing dementia.
  • Early‐onset (≤60‐year‐old) familial Alzheimer disease is caused by mutation in the APP, PSEN1 or PSEN2 gene in 30–50% of the families.
  • Late‐onset (>60 years old) Alzheimer disease have multifactorial inheritance.
  • Linkage and association studies have been largely unsuccessful, for reasons that include small sample size, low sensitivity to detect moderate effects and the substantial locus heterogeneity that underlies late‐onset Alzheimer disease.
  • The APOE ɛ4 allele is a major risk factor for late‐onset Alzheimer disease, while the ε2 allele has a protective effect.
  • Genome‐wide association studies indicate that BIN1, CRI, CLU and PICALM play a role in late‐onset Alzheimer disease.
  • Vascular dementia is the most common secondary brain disorder causing dementia.
  • Stroke is a syndrome and not a single disease and it is the stroke itself rather than the underlying vascular risk factors that cause the dementia.
  • CADASIL is the most common autosomal dominant inherited cause of stroke and vascular dementia caused by mutations in NOTCH3.

Keywords: Alzheimer disease; CADASIL; dementia; stroke; inheritance

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 Further Reading
    other The knowledge of genetics in dementia is expanding at a very fast pace, and for that reason textbooks will be outdated very fast. Thus, search engines such as MedLine, Ovid and/or PubMed with relevant search words is recommended.

Related Sub-Topics:

Neurobiology of Disease | Molecular Genetics of Common and Complex Disease | Genetics of Intelligence and Cognition
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Article Title: Genetics of Dementia
 
How to Cite close
Russell, Michael Bjørn(Jul 2012) Genetics of Dementia. In: eLS. John Wiley & Sons Ltd, Chichester. http://www.els.net [doi: 10.1002/9780470015902.a0023871]