Hostname: page-component-cd9895bd7-p9bg8 Total loading time: 0 Render date: 2024-12-22T19:55:07.441Z Has data issue: false hasContentIssue false

Association of the LRP1 gene and cognitive performance with amnestic mild cognitive impairment in elderly Chinese

Published online by Cambridge University Press:  10 August 2009

Yong M. Shi
Affiliation:
School of Clinical Medicine, Southeast University, Nanjing, China Department of Neurology, Affiliated ZhongDa Hospital of Southeast University, Nanjing, China
Hong Zhou
Affiliation:
School of Clinical Medicine, Southeast University, Nanjing, China Department of Neurology, Affiliated ZhongDa Hospital of Southeast University, Nanjing, China
Zhi J. Zhang*
Affiliation:
School of Clinical Medicine, Southeast University, Nanjing, China Department of Neurology, Affiliated ZhongDa Hospital of Southeast University, Nanjing, China
Hui Yu
Affiliation:
School of Clinical Medicine, Southeast University, Nanjing, China
Feng Bai
Affiliation:
School of Clinical Medicine, Southeast University, Nanjing, China
Yong G. Yuan
Affiliation:
School of Clinical Medicine, Southeast University, Nanjing, China Department of Psychiatry, Nanjing Brain Hospital, Nanjing, China
Ling L. Deng
Affiliation:
School of Clinical Medicine, Southeast University, Nanjing, China
Jian P. Jia
Affiliation:
Department of Neurology, XuanWu Hospital, Capital Medical University, Beijing, China
*
Correspondence should be addressed to: Zhi J. Zhang, M.D., Ph.D., Department of Neurology, affiliated ZhongDa Hospital of Southeast University, No. 87 DingJiaQiao Road, Nanjing, PR China, 210009. Phone: +86–25-83272023; Fax: +86–25-83272023. Email: [email protected].
Get access

Abstract

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.

Type
Research Article
Copyright
Copyright © International Psychogeriatric Association 2009

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

References

Aggarwal, N. T., Wilson, R. S., Beck, T. L., Bienias, J. L., Berry-Kravis, E. and Bennett, D. A. (2005). The apolipoprotein E epsilon4 and incident Alzheimer's disease in persons with mild cognitive impairment. Neurocase, 11, 37.CrossRefGoogle ScholarPubMed
Amieva, H. et al. (2004). Annual rate and predictors of conversion to dementia in subjects presenting mild cognitive impairment criteria defined according to a population-based study. Dementia and Geriatric Cognitive Disorders, 18, 8793.CrossRefGoogle ScholarPubMed
Bian, L. et al. (2005). Association study of the A2M and LRP1 genes with Alzheimer disease in the Han Chinese. Biological Psychiatry, 58, 731737.CrossRefGoogle ScholarPubMed
Cam, J. A., Zerbinatti, C. V., Li, Y. and Bu, G. (2005). Rapid endocytosis of the low density lipoprotein receptor-related protein modulates cell surface distribution and processing of the beta-amyloid precursor protein. Journal of Biological Chemistry, 280, 1546415470.CrossRefGoogle ScholarPubMed
Deng, Y., Sun, Y., Shi, J. J. and Zhang, S. Z. (2006). Meta-analysis of the association of the LRP C766T polymorphism with the risk of Alzheimer's disease. Hereditas, 28, 393398.Google ScholarPubMed
Dudbridge, F. (2008). Likelihood-based association analysis for nuclear families and unrelated subjects with missing genotype data. Human Heredity, 66, 8798.CrossRefGoogle ScholarPubMed
Egan, M. F. et al. (2003). The BDNF val66met polymorphism affects activity-dependent secretion of BDNF and human memory and hippocampal function. Cell, 112, 257269.CrossRefGoogle ScholarPubMed
Gabrieli, J. D. and Preston, A. R. (2003). Visualizing genetic influences on human brain functions. Cell, 112, 144145.CrossRefGoogle ScholarPubMed
Gainotti, G., Ferraccioli, M., Vita, M. G. and Marra, C. (2008). Patterns of neuropsychological impairment in MCI patients with small subcortical infarcts or hippocampal atrophy. Journal of the International Neuropsychological Society, 14, 611619.CrossRefGoogle ScholarPubMed
Gordon, N. G. (1972). The Trail Making Test in neuropsychological diagnosis. Journal of Clinical Psychology, 28, 167169.3.0.CO;2-X>CrossRefGoogle ScholarPubMed
Guarch, J., Marcos, T., Salamero, M. and Blesa, R. (2004). Neuropsychological markers of dementia in patients with memory complaints. International Journal of Geriatric Psychiatry, 19, 352358.CrossRefGoogle ScholarPubMed
Guo, Q. H., Lv, C. Z. and Hong, Z. (2001). The reliability and validity analysis of Auditory Verbal Learning Test. Chinese Mental Health Journal, 15, 1315.Google Scholar
Harris-White, M. E. and Frautschy, S. A. (2005). Low density lipoprotein receptor-related proteins (LRPs), Alzheimer's and cognition. Current Drug Targets – CNS & Neurological Disorders, 4, 469480.CrossRefGoogle ScholarPubMed
Hatanaka, Y. et al. (2000). Low density lipoprotein receptor-related protein gene polymorphisms and risk for late-onset Alzheimer's disease in a Japanese population. Clinical Genetics, 58, 319323.CrossRefGoogle Scholar
Herz, J. and Strickland, D. K. (2001). LRP: a multifunctional scavenger and signaling receptor. Journal of Clinical Investigation, 108, 779784.CrossRefGoogle ScholarPubMed
Ioannidis, J. P., Ntzani, E. E., Trikalinos, T. A. and Contopoulos-Ioannidis, D. G. (2001). Replication validity of genetic association studies. Nature Genetics, 29, 306309.CrossRefGoogle ScholarPubMed
Kang, D. E. et al. (1997). Genetic association of the low-density lipoprotein receptor-related protein gene (LRP), an apolipoprotein E receptor, with late-onset Alzheimer's disease. Neurology, 49, 5661.CrossRefGoogle ScholarPubMed
Katzman, R. et al. (1988). A Chinese version of the Mini-mental State Examination: impact of illiteracy in a Shanghai dementia survey. Journal of Clinical Epidemiology, 41, 971978.CrossRefGoogle Scholar
Lezak, M. D. (1983). Neuropsychological Assessment. 2nd edn (pp. 395402). New York: Oxford University Press.Google Scholar
Libon, D. J., Malamut, B. L., Swenson, R., Sands, L. P. and Cloud, B. S. (1996). Further analyses of clock drawings among demented and nondemented older subjects. Archives of Clinical Neuropsychology, 11, 193205.CrossRefGoogle ScholarPubMed
McKhann, G., Drachman, D., Folstein, M., Katzman, R., Price, D. and Stadlan, E. M. (1984). Clinical diagnosis of Alzheimer's disease: report of the NINCDS-ADRDA work group under the auspices of Department of Health and Human Services Task Force on Alzheimer's disease. Neurology, 34, 939944.CrossRefGoogle ScholarPubMed
Monsch, A. U., Bondi, M. W., Butters, N., Salmon, D. P., Katzman, R. and Thal, L. J. (1992). Comparisons of verbal fluency tasks in the detection of dementia of the Alzheimer type. Archives of Neurology, 49, 12531258.CrossRefGoogle ScholarPubMed
Morris, J. C. (1993). The Clinical Dementia Rating (CDR): current version and scoring rules. Neurology, 43, 24122414.CrossRefGoogle ScholarPubMed
Nutter-Upham, K. E. et al. (2008). Verbal fluency performance in amnestic MCI and older adults with cognitive complaints. Archives of Clinical Neuropsychology, 23, 229241.CrossRefGoogle ScholarPubMed
Panza, F. et al. (2004). Regional European differences in allele and genotype frequencies of low density lipoprotein receptor-related protein 1 polymorphism in Alzheimer's disease. American Journal of Medical Genetics Part B (Neuropsychiatric Genetics), 126B, 6973.CrossRefGoogle ScholarPubMed
Petersen, R. C. (2004). Mild cognitive impairment as a diagnostic entity, Journal of Internal Medicine, 256, 183194.CrossRefGoogle ScholarPubMed
Petersen, R. C., Smith, G. E., Waring, S. C., Ivnik, R. J., Tangalos, E. G. and Kokmen, E. (1999). Mild cognitive impairment: clinical characterization and outcome. Archives of Neurology, 56, 303308.CrossRefGoogle ScholarPubMed
Petersen, R. C. et al. (2001). Current concepts in mild cognitive impairment. Archives of Neurology, 58, 19851992.CrossRefGoogle ScholarPubMed
Rosen, W. G., Terry, R. D., Fuld, P. A., Katzman, R. and Peck, A. (1980). Pathological verification of ischemic score in differentiation of dementias. Annals of Neurology, 7, 486488.CrossRefGoogle ScholarPubMed
Shi, Y. Y. and He, L. (2005). SHEsis, a powerful software platform for analyses of linkage disequilibrium, haplotype construction, and genetic association at polymorphism loci. Cell Research, 15, 9798.CrossRefGoogle ScholarPubMed
Van, L. F. et al. (2001). Sequencing of the coding exons of the LRP1 and LDLR genes an individual DNA samples reveals novel mutations in both genes. Atherosclerosis, 154, 567577.Google Scholar
Wechsler, D. (1981). Wechsler Adult Intelligence Scale-Revised Manual. San Antonio, TX: Psychological Corp.Google Scholar
Zerbinatti, C. V. et al. (2006). Apolipoprotein E and low density lipoprotein receptor-related protein facilitate intraneuronal Abeta 42 accumulation in amyloid model mice. Journal of Biological Chemistry, 281, 3618036186.CrossRefGoogle ScholarPubMed