The association between the K-variant of the butyrylcholinesterase gene (BCHE-K) and Alzheimer disease (AD) or AD-related neuropathology has been reported to date with conflicting results. Here, we determined in a sample of 521 cases the severity of AD-related neuropathology and the polymorphisms of both BCHE-K and apolipoprotein E (ApoE). Histopathologically, all brains were classified according to procedures permitting differentiation of the evolutionary stages of neurofibrillary tangles (NFTs) and amyloid-beta-protein deposition (A beta-deposits). The results show that the association between BCHE-K and AD-related neuropathology only was limited to homozygotes for the K allele (P=0.036 for NFTs, and P=0.045 for A beta-deposits) at ages > or = 70 years but not 50-69 years. Furthermore, no interaction was apparent between BCHE-K and ApoE.