GENETIC ASSOCIATION OF THE LOW-DENSITY-LIPOPROTEIN RECEPTOR-RELATED PROTEIN GENE (LRP), AN APOLIPOPROTEIN-E RECEPTOR, WITH LATE-ONSET ALZHEIMERS-DISEASE

The presence of the APOE epsilon 4 allele encoding apolipoprotein E4 ( apoE4) is the major genetic risk factor for late-onset Alzheimer's dis ease (AD). However, the molecular and cellular mechanisms by which APO E epsilon 4 renders AD risk are unclear. In this report, we present ge netic evidence that an apoE receptor, LRP, may be associated with the expression of late-onset AD. Using a biallelic genetic marker in exon 3 of LRP, late-onset AD cases markedly differed from the control subje cts in the distribution of LRP genotypes, and this difference was high ly accentuated among AD cases with positive family history of senile d ementia. Furthermore, the numbers of neuritic plaques were significant ly altered as a consequence of different LRP genotypes in postmortem A D cases. Taken together, our results implicate the pathophysiology of LRP in the expression of late-onset AD.