Lipoprotein lipase mutations and Alzheimer's disease.

Lipoprotein lipase (LPL) helps transfer lipids from lipoprotein particles to cells. In the brain, LPL is present in Alzheimer's disease (AD) amyloid plaques. LPL binds apolipoprotein E (ApoE) lipoprotein particles and low-density lipoprotein receptor-related protein (LRP), an ApoE receptor. Since polymorphisms in both ApoE and LRP influence AD risk, we sought to determine whether LPL mutations also affect AD risk. In a case-control study, the frequencies of two of the most common known LPL mutations were measured in European-Americans either clinically diagnosed or pathologically confirmed as AD or normal control (N) subjects. In clinically diagnosed subjects, the Ser447Ter mutation comprised 9.8% (62/630) of alleles in N and 3.8% (9/238) in AD, a significant difference (P = 0.0057), while the Asn291Ser mutation comprised 1.1% (5/460) of alleles in N and 5.1% (8/158) in AD, also a significant difference (P = 0.0073), though in pathologically confirmed subjects the allele frequencies for AD did not significantly differ from N for either mutation. In clinically diagnosed subjects, LPL mutations were associated with altered AD risk, suggesting a potential role for LPL in the causation of AD. Further studies in different populations should help clarify the questions raised by these results.