LRP-1 variation is not associated with risk of Alzheimer's disease

Alzheimer's disease (AD) is characterised by the extensive deposition of amyloid beta (Aβ) within the parenchyma and vasculature of the brain. It is hypothesised that a dysfunction in Aβ degradation and/or its removal from the brain may result in accumulation as plaques. Low density lipoprotein receptor-related protein-1 (LRP-1) is a multifunctional receptor shown to be involved in cholesterol metabolism but also the removal of Aβ from the brain. Its ability to transport Aβ from the brain to the periphery has made it an attractive candidate for involvement in Alzheimer's disease (AD). We have assessed the frequencies of 9 tag- SNPs and the commonly studied synonymous SNP within exon 3 (rs1799986) in a multi-centre AD/control cohort and performed haplotype analysis. We found no evidence from a combined total of 412 controls and 1057 AD patients to support the involvement of LRP-1 variation, including the most commonly studied variant in rs1799986 in conferring genetic susceptibility to increased risk of AD.