The genotype 2/2 of the presenilin-1 polymorphism is decreased in Spanish early-onset Alzheimer's disease

We have found a significantly lower frequency of the presenilin-1 (PS-1) intronic polymorphism 2/2 genotype in early-onset Alzheimer's disease (AD) patients without APOE ϵ4 alleles (2/2=0.054; P=0.009) as compared to age matched non-ϵ4 controls (2/2=0.227). Moreover the average age of onset in AD patients with the PS-1 2/2 genotype is older than that in AD patients with a 1/2 genotype or with a 1/1 genotype. This data suggest a protective effect of the 2/2 genotype which would delay the age of onset in AD. Our results do not support an association between the 1/1 genotype and AD. However, a non-significant increase of the 1/1 genotype is found in non-ϵ4 AD patients (P=0.20).