ANALYSIS OF ALPHA-1 ANTICHYMOTRYPSIN, PRESENILIN-1, ANGIOTENSIN-CONVERTING ENZYME, AND METHYLENETETRAHYDROFOLATE REDUCTASE LOCI AS CANDIDATES FOR DEMENTIA

The genetic factors which predispose individuals to dementia in old ag e have not been fully defined, Although the apolipoprotein E4 allele a ccounts for a proportion of the genetic risk for late-onset Alzheimer disease (AD), it is neither necessary nor sufficient to cause this dis ease, Recent suggestions that other loci are involved in dementia risk have been supported by findings of associations of genotypes at the a lpha-1 antichymotrypsin (ACT) and presenilin-1 (PS-1) loci with AD, We investigated these loci in two community-based aged Cambridgeshire po pulations: the rural Ely population (cohort 1) comprised 60 pairs of d emented and nondemented elderly individuals, with a mean age of 84.2 y ears; and the Cambridge city population (cohort 2) comprised 81 pairs all over age 84, with a mean age of 87.3 years. Since vascular risk fa ctors are likely to impact on dementia risk, we also examined the angi otensin-converting enzyme (ACE) and methylenetetrahydrofolate reductas e (MTHFR) genes as candidates, ACE, ACT, PS-1, and MTHFR genotype and allele frequencies were not significantly different in cases and match ed controls, These data support the doubts which have been raised abou t the involvement of the PS-1 and ACT polymorphisms in late-onset deme ntia. (C) 1997 Wiley-Lies, Inc.