Association study and meta-analysis of low-density lipoprotein receptor related protein in Alzheimer's disease

Pritchard, Antonia, Harris, Judith, Pritchard, Colin W., St. Clair, David, Lemmon, Helen, Lambert, Jean-Charles, Chartier-Harlin, Marie-Christine, Hayes, Angela, Thaker, Uma, Iwatsubo, Takeshi, Mann, David M. A. and Lendon, Corinne (2005) Association study and meta-analysis of low-density lipoprotein receptor related protein in Alzheimer's disease. Neuroscience Letters, 382 3: 221-226. doi:10.1016/j.neulet.2005.03.016

Author Pritchard, Antonia
Harris, Judith
Pritchard, Colin W.
St. Clair, David
Lemmon, Helen
Lambert, Jean-Charles
Chartier-Harlin, Marie-Christine
Hayes, Angela
Thaker, Uma
Iwatsubo, Takeshi
Mann, David M. A.
Lendon, Corinne
Title Association study and meta-analysis of low-density lipoprotein receptor related protein in Alzheimer's disease
Journal name Neuroscience Letters   Check publisher's open access policy
ISSN 0304-3940
Publication date 2005-07-15
Sub-type Article (original research)
DOI 10.1016/j.neulet.2005.03.016
Volume 382
Issue 3
Start page 221
End page 226
Total pages 6
Place of publication Amsterdam, Netherlands
Publisher Elsevier Ireland
Language eng
Subject 1109 Neurosciences
Formatted abstract
Genome scans in sporadic Alzheimer's disease (AD) have revealed a possible susceptibility locus on chromosome 12. The low density lipoprotein receptor related protein (LRP1) gene lies within this area of linkage. Eighteen previous AD case-control studies have investigated the C766T polymorphism in LRP1 with conflicting results, including a protective effect on AD of the T allele, an increased susceptibility towards AD with both the C and T alleles, or no association at all. We have now performed a case-control study based on a large UK cohort of 477 AD patients and 466 matched controls, and have included these data, with those drawn from the 18 previous studies, into in a meta-analysis of 4668 AD patients and 4473 controls. We find no evidence for influence on the risk for AD in either our own present cohort or in the combined data set. Furthermore, we investigated whether the C766T polymorphism might modify the clinical and pathological phenotype in our cohort. We found no association with AD when the cohort was stratified into those with early (<65 years) or late (>65 years) onset, or when split into Apolipoprotein E (APOE) ε4 bearers and ε4 non-bearers. In addition, the C766T polymorphism was shown not to influence the age onset of AD. In a separate autopsy-confirmed cohort of 130 AD cases, no association with genotype or allele was observed for tissue levels of β-amyloid 40, β-amyloid 42, total β-amyloid, pathological tau proteins, microglial cells or extent of astrocytic activity. Therefore, in this present study, we find no evidence for the involvement of this polymorphism either in increasing the susceptibility to AD, or by acting as a phenotypic modifier.
© 2005 Published by Elsevier Ireland Ltd.
Keyword Alzheimer's disease
Brain pathology
Association study
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status Non-UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: Excellence in Research Australia (ERA) - Collection
School of Medicine Publications
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