Low-density lipoprotein receptor-related protein 8 (apolipoprotein E receptor 2) gene polymorphisms in Alzheimer's disease

Apolipoprotein E (ApoE) isoforms affect the risk of developing Alzheimer's disease (AD). ApoE-associated risk may be related to its binding to and clearance by cell surface receptors, such as the members of the low-density lipoprotein (LDL) receptor family. Previous studies had shown association of LDL receptor-related protein (LRP) and AD, therefore we speculated that another member of this LDL receptor family, LRP8 (also called apolipoprotein E receptor 2 or ApoER2), which is predominantly expressed in brain, might be associated with Alzheimer's disease. To explore this hypothesis, we screened exons 2–19 of the LRP8 gene in a total of 204 AD and 184 elderly control subjects for polymorphisms using the conformation-sensitive gel electrophoresis method. Our results revealed four sequence alterations: two predicted to result in amino acid changes (E46D and R952Q), one in an intron (IVS9+7G>A), and one synonymous polymorphism (2622T>C). The latter was found in four AD patients (2.0%) and 11 controls (6.0%), a significant difference ( P=0.042). Further study is needed to confirm this possible association of LRP8 with AD.