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.
Ma
Suk Ling
SL
Department of Anatomical and Cellular Pathology, Faculty of Medicine, The Chinese University of Hong Kong, Shatin, Hong Kong, China.
Ng
Ho Keung
HK
Baum
Larry
L
Pang
Jesse Chung Sean
JC
Chiu
Helen Fung Kum
HF
Woo
Jean
J
Tang
Nelson Leung Sang
NL
Lam
Linda Chiu Wa
LC
D000368:Aged; D000544:Alzheimer Disease / Q000235:genetics*; D017931:DNA Primers; D004591:Electrophoresis, Polyacrylamide Gel; D005091:Exons / Q000235:genetics; D005260:Female; D006801:Humans; D007438:Introns / Q000235:genetics; D026502:LDL-Receptor Related Proteins; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D011110:Polymorphism, Genetic / Q000235:genetics*; D018110:Receptors, Lipoprotein / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction
D017931:DNA Primers; D026502:LDL-Receptor Related Proteins; D018110:Receptors, Lipoprotein; C098773:low density lipoprotein receptor-related protein 8