Association of the LRP1 gene and cognitive performance with amnestic mild cognitive impairment in elderly Chinese.
BACKGROUND
The genetic region coding for low-density lipoprotein receptor-related protein1 (LRP1) is considered an intriguing susceptibility locus for Alzheimer's disease (AD). Amnestic mild cognitive impairment (aMCI) is characterized by episodic memory impairment and represents the prodromal stage of AD. Our aim in this study is to investigate the relationship between LRP1 genetic variation and aMCI, and the influence of LRP1 on cognitive performance.


METHODS
We performed a case-control association study analyzing five polymorphisms in LRP1 gene by TaqMan Assays-on-Demand SNP Genotyping. All samples were derived from Chinese subjects (109 cases, 104 healthy controls) and assessed using multi-dimension neuropsychological instruments.


RESULTS
We identified haplotypes within the region containing the LRP1 gene. Of these, haplotype TAA (T: rs1800194; A: rs11837145; A: rs10876967) was significantly associated with aMCI, being over-represented in aMCI versus healthy controls. Haplotype TAA was associated with poor performance on episodic memory in all subjects.


CONCLUSIONS
This study confirms the association between genetic variants in LRP1 and aMCI. Moreover, we have identified a relationship between LRP1 genetic variation and specific aspects of neurocognitive function. Our convergent results suggest that LRP1 plays an important role in cognitive function and possibly in the pathogenesis of aMCI.
Shi
Yong M
YM
School of Clinical Medicine, Southeast University, Nanjing, China.
Zhou
Hong
H
Zhang
Zhi J
ZJ
Yu
Hui
H
Bai
Feng
F
Yuan
Yong G
YG
Deng
Ling L
LL
Jia
Jian P
JP
D000368:Aged; D000369:Aged, 80 and over; D000483:Alleles; D000544:Alzheimer Disease / Q000235:genetics*; D000647:Amnesia / Q000175:diagnosis / Q000235:genetics*; D016022:Case-Control Studies; D002681:China; D003072:Cognition Disorders / Q000175:diagnosis / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease / Q000235:genetics; D005838:Genotype; D006239:Haplotypes; D006801:Humans; D026503:Low Density Lipoprotein Receptor-Related Protein-1 / Q000235:genetics*; D008297:Male; D009483:Neuropsychological Tests / Q000706:statistics & numerical data*; D010641:Phenotype; D011110:Polymorphism, Genetic / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D011594:Psychometrics
D026503:Low Density Lipoprotein Receptor-Related Protein-1