Low-density lipoprotein receptor-related protein 8 gene polymorphisms and dementia

The sole known genetic risk factor for sporadic Alzheimer's disease (AD) is the gene encoding apolipoprotein E (APOE), but the underlying mechanism is still under debate. One hypothesis relies on an interaction between APOE and its receptors. Previous studies have shown association of LDL receptor-related protein (LRP1) with AD and we previously reported a modulation by LRP1 of the risk of AD conferred by the −499A > G promoter polymorphism of the MAPK8IP1, a gene encoding Islet-brain-1 (IB1), the human counterpart of c-Jun NH2 terminal kinase interacting protein-1 (JIP-1). Here we tested in two independent population samples a possible impact of another receptor for APOE, namely the low-density lipoprotein receptor-related protein 8 (LRP8), on the risk of dementia. Our results did not reveal any direct impact of a LRP8 coding (Arg952Gln) mutation on the risk of AD. However, this polymorphism increased the risk of AD conferred by the MAPK8IP1 G allele.