Genetic and host factors for dementia in Down's syndrome

Abstract

Background: The high risk for dementia in adults with Down's syndrome has been attributed to triplication and overexpression of the gene for amyloid precursor protein (APP). But the wide variation in age at onset must be due to other risk factors. Aims: To identify factors which influence age at onset of dementia in Down's syndrome. Method: Studies of factors which influence formation of beta-amyloid (Aβ) were reviewed, including atypical karyotypes, susceptibility genotypes, gender and oestrogen deficiency, and individual differences in Aβ peptide levels. Results: The apolipoprotein E ε4 allele, oestrogen deficiency and high levels of Aβ1-42 peptide are associated with earlier onset of dementia, while atypical karyotypes and the apolipoprotein E ε2 allele are associated with reduced mortality and reduced risk of dementia. Conclusions: Factors which influence Aβ levels, rather than overexpression of APP, may account for the differences in age at onset of dementia in Down's syndrome.