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

A Pritchard, J Harris, C W Pritchard, D St Clair, H Lemmon, J C Lambert, M C Chartier-Harlin, A Hayes, U Thaker, T Iwatsubo, D M A Mann, C Lendon

Research output: Contribution to journalArticle

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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) epsilon 4 bearers and 64 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 beta-amyloid 40, P-amyloid 42, total beta-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. (c) 2005 Published by Elsevier Ireland Ltd.

Original languageEnglish
Pages (from-to)221-226
Number of pages6
JournalNeuroscience Letters
Volume382
DOIs
Publication statusPublished - 2005

Keywords

  • Alzheimer's disease
  • LRP1
  • meta-analysis
  • brain pathology
  • association study
  • APOLIPOPROTEIN-E
  • LRP GENE
  • EXON 3
  • CANDIDATE GENES
  • RISK-FACTORS
  • HUMAN BRAIN
  • POLYMORPHISM
  • POPULATION
  • BETA
  • ALPHA-2-MACROGLOBULIN

Cite this

Association study and meta-analysis of low-density lipoprotein receptor related protein in Alzheimer's disease. / Pritchard, A ; Harris, J ; Pritchard, C W ; St Clair, D ; Lemmon, H ; Lambert, J C ; Chartier-Harlin, M C ; Hayes, A ; Thaker, U ; Iwatsubo, T ; Mann, D M A ; Lendon, C .

In: Neuroscience Letters, Vol. 382, 2005, p. 221-226.

Research output: Contribution to journalArticle

Pritchard, A, Harris, J, Pritchard, CW, St Clair, D, Lemmon, H, Lambert, JC, Chartier-Harlin, MC, Hayes, A, Thaker, U, Iwatsubo, T, Mann, DMA & Lendon, C 2005, 'Association study and meta-analysis of low-density lipoprotein receptor related protein in Alzheimer's disease', Neuroscience Letters, vol. 382, pp. 221-226. https://doi.org/10.1016/j.neulet.2005.03.016
Pritchard, A ; Harris, J ; Pritchard, C W ; St Clair, D ; Lemmon, H ; Lambert, J C ; Chartier-Harlin, M C ; Hayes, A ; Thaker, U ; Iwatsubo, T ; Mann, D M A ; Lendon, C . / Association study and meta-analysis of low-density lipoprotein receptor related protein in Alzheimer's disease. In: Neuroscience Letters. 2005 ; Vol. 382. pp. 221-226.
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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) epsilon 4 bearers and 64 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 beta-amyloid 40, P-amyloid 42, total beta-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. (c) 2005 Published by Elsevier Ireland Ltd.",
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AU - Pritchard, A

AU - Harris, J

AU - Pritchard, C W

AU - St Clair, D

AU - Lemmon, H

AU - Lambert, J C

AU - Chartier-Harlin, M C

AU - Hayes, A

AU - Thaker, U

AU - Iwatsubo, T

AU - Mann, D M A

AU - Lendon, C

PY - 2005

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N2 - 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) epsilon 4 bearers and 64 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 beta-amyloid 40, P-amyloid 42, total beta-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. (c) 2005 Published by Elsevier Ireland Ltd.

AB - 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) epsilon 4 bearers and 64 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 beta-amyloid 40, P-amyloid 42, total beta-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. (c) 2005 Published by Elsevier Ireland Ltd.

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KW - LRP1

KW - meta-analysis

KW - brain pathology

KW - association study

KW - APOLIPOPROTEIN-E

KW - LRP GENE

KW - EXON 3

KW - CANDIDATE GENES

KW - RISK-FACTORS

KW - HUMAN BRAIN

KW - POLYMORPHISM

KW - POPULATION

KW - BETA

KW - ALPHA-2-MACROGLOBULIN

U2 - 10.1016/j.neulet.2005.03.016

DO - 10.1016/j.neulet.2005.03.016

M3 - Article

VL - 382

SP - 221

EP - 226

JO - Neuroscience Letters

JF - Neuroscience Letters

SN - 0304-3940

ER -