Lipoprotein lipase mutations and Alzheimer's disease

✍ Scribed by Baum, Larry; Chen, Lan; Masliah, Eliezer; Chan, Yuen Shan; Ng, Ho-Keung; Pang, Chi Pui

• Publisher: John Wiley and Sons
• Year: 1999
• Tongue: English
• Weight: 12 KB
• Volume: 88
• Category: Article
• ISSN: 0148-7299
• DOI: 10.1002/(sici)1096-8628(19990416)88:2<136::aid-ajmg8>3.0.co;2-d

✦ Synopsis

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. Am.