α2-Macroglobulin, lipoprotein receptor-related protein and lipoprotein receptor-associated protein and the genetic risk for developing Alzheimer's disease

Candan Depboylu, Frank Lohmüller, Yansheng Du, Matthias Riemenschneider, Alexander Kurz, Thomas Gasser, Ulrich Müller, Richard C. Dodel

Research output: Contribution to journalArticle

16 Citations (Scopus)

Abstract

α2-Macroglobulin (α2M) as well as its receptor, the low-density lipoprotein receptor-related (LRP) and the receptor-associated protein (RAP) are involved in the clearance of cerebral Aβ. Current evidence suggests that polymorphisms in the genes of α2M, LRP and RAP may have functional effects on the proteins. Two independent association samples of 271 AD patients and 280 representative controls were investigated whether the risk for developing AD is altered in carriers of polymorphisms in the α2M-gene (Va1000Ile), in the LRP-gene (Ala216Val) and in the RAP-gene (Val311Met). Genotypes were determined by standard PCR and restriction fragment length polymorphism. The results were adjusted for age, gender and apolipoprotein E-ε4 (APOE) polymorphism. Inheritance of α2M conferred a small increased risk for sporadic AD with an estimated Mantel-Haenszel odds ratio of 1.47. There was no age- or gender-dependent increase in α2M Val1000Ile allele frequencies in AD patients compared to controls. There was no significant difference in the allele frequencies among control and AD subjects for the LRP and RAP polymorphisms. We found no evidence of an interaction between the α2M and RAP or LRP with regard to conferred risk. Our data suggest that the α2M Val1000Ile polymorphism is weakly associated with AD. Although LRP as well as RAP seem to play an essential role in the metabolism of α2M and APOE, there is no increase in the genetic risk for AD in patients carrying the investigated polymorphisms.

Original languageEnglish
Pages (from-to)187-190
Number of pages4
JournalNeuroscience Letters
Volume400
Issue number3
DOIs
StatePublished - Jun 12 2006

Fingerprint

Lipoprotein Receptors
Macroglobulins
Alzheimer Disease
Proteins
Apolipoprotein E4
Gene Frequency
Genes
Patient Advocacy
LDL Receptors
Restriction Fragment Length Polymorphisms
Odds Ratio
Genotype
Polymerase Chain Reaction

Keywords

  • Amyloid
  • Dementia
  • Inflammation
  • Lipoprotein
  • Polymorphism

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

α2-Macroglobulin, lipoprotein receptor-related protein and lipoprotein receptor-associated protein and the genetic risk for developing Alzheimer's disease. / Depboylu, Candan; Lohmüller, Frank; Du, Yansheng; Riemenschneider, Matthias; Kurz, Alexander; Gasser, Thomas; Müller, Ulrich; Dodel, Richard C.

In: Neuroscience Letters, Vol. 400, No. 3, 12.06.2006, p. 187-190.

Research output: Contribution to journalArticle

Depboylu, Candan ; Lohmüller, Frank ; Du, Yansheng ; Riemenschneider, Matthias ; Kurz, Alexander ; Gasser, Thomas ; Müller, Ulrich ; Dodel, Richard C. / α2-Macroglobulin, lipoprotein receptor-related protein and lipoprotein receptor-associated protein and the genetic risk for developing Alzheimer's disease. In: Neuroscience Letters. 2006 ; Vol. 400, No. 3. pp. 187-190.
@article{212950724b824a0a908b4af5dedc7ac9,
title = "α2-Macroglobulin, lipoprotein receptor-related protein and lipoprotein receptor-associated protein and the genetic risk for developing Alzheimer's disease",
abstract = "α2-Macroglobulin (α2M) as well as its receptor, the low-density lipoprotein receptor-related (LRP) and the receptor-associated protein (RAP) are involved in the clearance of cerebral Aβ. Current evidence suggests that polymorphisms in the genes of α2M, LRP and RAP may have functional effects on the proteins. Two independent association samples of 271 AD patients and 280 representative controls were investigated whether the risk for developing AD is altered in carriers of polymorphisms in the α2M-gene (Va1000Ile), in the LRP-gene (Ala216Val) and in the RAP-gene (Val311Met). Genotypes were determined by standard PCR and restriction fragment length polymorphism. The results were adjusted for age, gender and apolipoprotein E-ε4 (APOE) polymorphism. Inheritance of α2M conferred a small increased risk for sporadic AD with an estimated Mantel-Haenszel odds ratio of 1.47. There was no age- or gender-dependent increase in α2M Val1000Ile allele frequencies in AD patients compared to controls. There was no significant difference in the allele frequencies among control and AD subjects for the LRP and RAP polymorphisms. We found no evidence of an interaction between the α2M and RAP or LRP with regard to conferred risk. Our data suggest that the α2M Val1000Ile polymorphism is weakly associated with AD. Although LRP as well as RAP seem to play an essential role in the metabolism of α2M and APOE, there is no increase in the genetic risk for AD in patients carrying the investigated polymorphisms.",
keywords = "Amyloid, Dementia, Inflammation, Lipoprotein, Polymorphism",
author = "Candan Depboylu and Frank Lohm{\"u}ller and Yansheng Du and Matthias Riemenschneider and Alexander Kurz and Thomas Gasser and Ulrich M{\"u}ller and Dodel, {Richard C.}",
year = "2006",
month = "6",
day = "12",
doi = "10.1016/j.neulet.2006.01.040",
language = "English",
volume = "400",
pages = "187--190",
journal = "Neuroscience Letters",
issn = "0304-3940",
publisher = "Elsevier Ireland Ltd",
number = "3",

}

TY - JOUR

T1 - α2-Macroglobulin, lipoprotein receptor-related protein and lipoprotein receptor-associated protein and the genetic risk for developing Alzheimer's disease

AU - Depboylu, Candan

AU - Lohmüller, Frank

AU - Du, Yansheng

AU - Riemenschneider, Matthias

AU - Kurz, Alexander

AU - Gasser, Thomas

AU - Müller, Ulrich

AU - Dodel, Richard C.

PY - 2006/6/12

Y1 - 2006/6/12

N2 - α2-Macroglobulin (α2M) as well as its receptor, the low-density lipoprotein receptor-related (LRP) and the receptor-associated protein (RAP) are involved in the clearance of cerebral Aβ. Current evidence suggests that polymorphisms in the genes of α2M, LRP and RAP may have functional effects on the proteins. Two independent association samples of 271 AD patients and 280 representative controls were investigated whether the risk for developing AD is altered in carriers of polymorphisms in the α2M-gene (Va1000Ile), in the LRP-gene (Ala216Val) and in the RAP-gene (Val311Met). Genotypes were determined by standard PCR and restriction fragment length polymorphism. The results were adjusted for age, gender and apolipoprotein E-ε4 (APOE) polymorphism. Inheritance of α2M conferred a small increased risk for sporadic AD with an estimated Mantel-Haenszel odds ratio of 1.47. There was no age- or gender-dependent increase in α2M Val1000Ile allele frequencies in AD patients compared to controls. There was no significant difference in the allele frequencies among control and AD subjects for the LRP and RAP polymorphisms. We found no evidence of an interaction between the α2M and RAP or LRP with regard to conferred risk. Our data suggest that the α2M Val1000Ile polymorphism is weakly associated with AD. Although LRP as well as RAP seem to play an essential role in the metabolism of α2M and APOE, there is no increase in the genetic risk for AD in patients carrying the investigated polymorphisms.

AB - α2-Macroglobulin (α2M) as well as its receptor, the low-density lipoprotein receptor-related (LRP) and the receptor-associated protein (RAP) are involved in the clearance of cerebral Aβ. Current evidence suggests that polymorphisms in the genes of α2M, LRP and RAP may have functional effects on the proteins. Two independent association samples of 271 AD patients and 280 representative controls were investigated whether the risk for developing AD is altered in carriers of polymorphisms in the α2M-gene (Va1000Ile), in the LRP-gene (Ala216Val) and in the RAP-gene (Val311Met). Genotypes were determined by standard PCR and restriction fragment length polymorphism. The results were adjusted for age, gender and apolipoprotein E-ε4 (APOE) polymorphism. Inheritance of α2M conferred a small increased risk for sporadic AD with an estimated Mantel-Haenszel odds ratio of 1.47. There was no age- or gender-dependent increase in α2M Val1000Ile allele frequencies in AD patients compared to controls. There was no significant difference in the allele frequencies among control and AD subjects for the LRP and RAP polymorphisms. We found no evidence of an interaction between the α2M and RAP or LRP with regard to conferred risk. Our data suggest that the α2M Val1000Ile polymorphism is weakly associated with AD. Although LRP as well as RAP seem to play an essential role in the metabolism of α2M and APOE, there is no increase in the genetic risk for AD in patients carrying the investigated polymorphisms.

KW - Amyloid

KW - Dementia

KW - Inflammation

KW - Lipoprotein

KW - Polymorphism

UR - http://www.scopus.com/inward/record.url?scp=33646265052&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=33646265052&partnerID=8YFLogxK

U2 - 10.1016/j.neulet.2006.01.040

DO - 10.1016/j.neulet.2006.01.040

M3 - Article

C2 - 16650578

AN - SCOPUS:33646265052

VL - 400

SP - 187

EP - 190

JO - Neuroscience Letters

JF - Neuroscience Letters

SN - 0304-3940

IS - 3

ER -