Synergy between the genes for butyrylcholinesterase K variant and apolipoprotein E4 in late-onset confirmed Alzheimer's disease

The allelic frequency of the gene for the K variant ofbutyrylcholinesterase (BCHE-K) was 0.17 in 74 subjects with late-onset (age> 65 years) histopathologically diagnosed Alzheimer's disease (AD),which was higher than the frequencies in 104 elderly control subjects(0.09), in 14 early-onset cases of confirmed AD (0.07) and in 29 confirmedcases of other dementia (0.10). The association of BCHE-K with late-onsetAD was limited to carriers of the epsilon 4 allele of the apolipoprotein Egene (APOE), among whom the presence of BCHE-K gave an odds ratio ofconfirmed late-onset AD of 6.9 (95% C.I. 1.65-29) in subjects > 65 yearsand of 12.8 (1.9-86) in subjects > 75 years. In APOE epsilon 4 carriersover 75 years, only 1/22 controls, compared with 10/24 confirmed late-onsetAD cases, had BCHE-K. We suggest that BCHE-K, or a nearby gene onchromosome 3, acts in synergy with APOE epsilon 4 as a susceptibility genefor late-onset AD.