Is the LDL receptor-related protein involved in Alzheimer's disease?
LDL-related protein receptor (LRP) is the main receptor in the brain for apolipoprotein E. Moreover, the LRP gene is located on chromosome 12, the site of a potential Alzheimer's disease (AD) locus. We explored the association between the LRP gene and AD in 600 French Caucasian patients (37.8% men, mean age 72.0+/-8.0 years, mean age at onset 68.7+/-8.1 years) and age-matched controls (n=646, 37.0% men, mean age 72.5+/-8.2 years) and observed an association between a (TTTC) repeat at the 3' end of an Alu sequence in the LRP gene and the risk of developing AD. Three alleles were detected in this population [corresponding to 83, 87, and 91 base pairs (bp)], the 91-bp allele being associated with an increased risk of developing AD [all patients: odds ratio (OR) 1.6, P<0.01; late-onset AD: OR 1.8, P<0.01]. This suggests an association between the LRP locus and AD. However, in the light of studies related to the exon 3 LRP polymorphism and given the low strength of the association reported here, a biologically active variant may exist on chromosome 12, either in the LRP gene itself or in another gene in the vicinity.
Lambert
J C
JC
Service d'Epidémiologie et de Santé Publique - INSERM U.508, Institut Pasteur de Lille, 1 rue Calmette, F-59019 Lille Cedex, France.
Chartier-Harlin
M C
MC
Cottel
D
D
Richard
F
F
Neuman
E
E
Guez
D
D
Legrain
S
S
Berr
C
C
Amouyel
P
P
Helbecque
N
N
D017668:Age of Onset; D000368:Aged; D000544:Alzheimer Disease / Q000235:genetics* / Q000378:metabolism; D001921:Brain / Q000378:metabolism*; D002881:Chromosomes, Human, Pair 12; D015331:Cohort Studies; D005260:Female; D005602:France; D005787:Gene Frequency; D005838:Genotype; D006801:Humans; D026503:Low Density Lipoprotein Receptor-Related Protein-1; D008297:Male; D011971:Receptors, Immunologic / Q000235:genetics*; D011973:Receptors, LDL / Q000378:metabolism; D012016:Reference Values; D044465:White People
D026503:Low Density Lipoprotein Receptor-Related Protein-1; D011971:Receptors, Immunologic; D011973:Receptors, LDL