Genetics of Alzheimer’s disease — routes to the pathophysiology
Considerable advances have been made the last years in the understanding of the pathogenesis of Alzheimer’s disease (AD): Several pathogenic mutations have been found in the amyloid precursor protein gene on chromosome 21. Two other dominantly operating genes on chromosome 14 and 1 were recently cloned, named presenilin 1 and 2, respectively. Mutations in these genes give rise to AD with a very early age of onset. Increased Aβ1-42 is most likely the pathogenic mechanism in all these cases. A susceptibility gene for AD has also been found. There is an association between the ɛ4 allele of the apolipoprotein E (APOE) gene and late-onset AD. The ɛ4 allele increases the risk for AD, although some ɛ4 homozygotes may live a long life without developing AD. The mechanism by which APOE ɛ4 promotes development of AD is most likely increased plaque formation. The new knowledge on pathogenic mechanisms of the disease gives opportunities for alternative strategies for therapeutic intervention.
KeywordsAmyloid Precursor Protein Amyloid Precursor Protein Processing Amyloid Precursor Protein Gene Amyloid Precursor Protein Mutation Presenilin Mutation
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