Lipoprotein lipase mutations and Alzheimer's disease

Lipoprotein lipase (LPL) helps transfer lipids from lipoprotein particles t o cells. In the brain, LPL is present in Alzheimer's disease (AD) amyloid p laques, LPL binds apolipoprotein E (ApoE) lipoprotein particles and low-den sity lipoprotein receptor-related protein (LRP), an ApoE receptor. Since po lymorphisms in both ApoE and LRP influence AD risk, we sought to determine whether LPL mutations also affect AD risk. In a ease-control study, the fre quencies of two of the most common known LPL mutations were measured in Eur opean-Americans either clinically diagnosed or pathologically confirmed as AD or normal control (N) subjects. In clinically diagnosed subjects, the Se r447Ter mutation comprised 9.8% (62/630) of alleles in N and 3.8% (9/238) i n AD, a significant difference (P = 0.0057), while the Asn291Ser mutation c omprised 1.1% (5/460) of alleles in N and 5.1% (8/158) in AD, also a signif icant difference (P = 0.0073), through in pathologically confirmed subjects the allele frequencies for AD did not significantly differ from N for eith er mutation. In clinically diagnosed subjects, LPL mutations were associate d with altered AD risk, suggesting a potential role for LPL in the causatio n of AD, Further studies in different populations should help clarify the q uestions raised by these results. (C) 1999 Wiley-Liss, Inc.