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Aetiology

Last edited Mar 2, 2024. Last reviewed Mar 2, 2024

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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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Aetiology

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