[Genetic complexity of Alzheimer's disease].

The discovery of pathogenic mutations in the amyloid precursor protein (APP) gene and the presenilin (PS1, PS2) genes, causing familial early-onset AD has lead to the hypothesis of the amyloid cascade. The epsilon4 allele of the apolipoprotein E (APOE) gene, the only recognized genetic risk factor for AD, may be involved in the mechanism. However, to date, search for new genetic determinants has been hampered by methodological limitations.

Association study of Notch 4 polymorphisms with Alzheimer's disease.

Background: The NOTCH4 gene is located at 6p21.3, a site shown in several studies to have significant linkage with Alzheimer's disease.

Objective: To investigate the potential impact of two polymorphisms within this gene on the risk of developing Alzheimer's disease.

No association of the HLA-A2 allele with Alzheimer's disease.

A possible association of the human leucocyte antigen (HLA)-A2 allele with increased susceptibility to Alzheimer's disease (AD) has been the subject of debate for more than 20 years. We compared the presence of the HLA-A2 allele in a sample from the French population composed of 451 patients and 477 controls. There was no evidence of an association of this allele with increased risk of AD.

No association of the -48CT polymorphism of the presenilin 1 gene with Alzheimer disease in a late-onset sporadic population.

Recently, a polymorphism located in the promoter of the presenilin 1 gene was associated with early-onset Alzheimer disease (EOAD). To determine if this polymorphism is also a risk factor for late-onset Alzheimer's disease (LOAD), we analysed its potential impact in a French population of LOAD patients only. Genotype and allelic distributions of the -48CT polymorphism were similar for controls and AD patients.

Contribution of APOE promoter polymorphisms to Alzheimer's disease risk.

Objective: To determine whether the effects of APOE promoter polymorphisms on AD are independent of the APOE-epsilon4 allele.

Background: Recently, the -491 A-->T and -219 G-->T polymorphisms located in the APOE promoter have been suggested to be risk factors for AD. However, the effects of these polymorphisms have not always been reproduced in case-control studies, possibly because of the strong linkage disequilibrium existing at this locus or the characteristics of the populations studied.