Results from various genetic association studies of the lipoprotein lipase (LPL) S447X polymorphism and Alzheimer's disease (AD), range from a statistically significant negative association of clinically examined patients to a non-significant but consistent trend for under-representation of the X447 allele in neuropathologically confirmed subjects. In this report we have compared the distribution of the above polymorphism in an independent group of clinically diagnosed AD patients, including a subgroup where the disease was pathologically confirmed, and a spousal control group. No statistically significant differences emerged from this comparison. We conclude that LPL cannot be a major factor in pathogenesis of AD.