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 (LRPI) with AD and We previously reported a modulation by LRPI of the risk of AD conferred by the -499A>G promoter polymorphism of the MAPK8IP1, a gene encoding Islet-brain-I (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 an), direct impact of a LRP8 coding (Arg952Gln) mutation on the risk of AD. However, (his polymorphism increased the risk of AD conferred by the MAPK8IP1 G allele. (C) 2007 Elsevier Inc. All rights reserved.