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Aetiology

Last reviewed dd mmm yyyy. Last edited dd mmm yyyy

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Environmental factors which predispose to Alzheimer's disease include:

  • a history of head injury
  • low educational attainment
  • there is evidence that increased plasma homocysteine levels is a risk factor for Alzheimer's disease (1,2)
  • type 2 diabetes (T2D) has been associated with a modest increased risk in cognitive dysfunction across all cognitive domains (1,3)
    • effect appears to be consistent across all age groups and mimics an accelerated ageing of brain function - however there is also an increased risk of more severe impairment of cognition and developing dementia in older age groups that would appear to be a different phenomenon (3).

Three genes have been linked to the pathogenesis of Alzheimer's disease (4):

  • beta-amyloid precursor protein:
    • chromosome 21
    • specific mutations result in familial Alzheimer's disease with onset in the sixth decade
    • proteolytic processing of the mutant protein favours the formation of the amyloidogenic A-beta fragment
  • apolipoprotein E4:
    • chromosome 19
    • the E4 allele increases the risk of Alzheimer's disease and reduces the mean age of onset
    • the E2 allele protects against Alzheimer's disease
  • presenilin 1:
    • transmembrane protein which is mutated in some forms of familial Alzheimer's disease
    • increases the proportion of amyloidogenic peptides derived from beta-amyloid precursor protein
    • may be involved in apoptosis
    • gene on chromosome 14
  • presenilin 2:
    • homologous in structure and function to presenilin 1
    • gene on chromosome 1.

Reference:

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