Is alpha-T catenin (VR22) an Alzheimer's disease risk gene?

Background: Recently, conflicting reports have been published on the potential role of genetic variants in the alpha-T catenin gene (VR22; CTNNA3) on the risk for Alzheimer's disease. In these papers, evidence for association is mostly observed in multiplex families with Alzheimer's disease, whereas case-control samples of sporadic Alzheimer's disease are predominantly negative.

Methods: After sequencing VR22 in multiplex families with Alzheimer's disease linked to chromosome 10q21, we identified a novel non-synonymous (Ser596Asn; rs4548513) single nucleotide polymorphism (SNP).

Genetic association of Alzheimer's disease with multiple polymorphisms in alpha-2-macroglobulin.

Alpha-2-Macroglobulin (A2M) is a highly plausible candidate gene for Alzheimer's disease (AD) in a region of chromosome 12 that has numerous independent reports of genetic linkage. We previously reported that a 5 bp deletion in A2M was associated with AD in a subset of the National Institute of Health (NIMH) Genetics Initiative AD family sample. Efforts to replicate this association finding in case - control samples have been largely negative, while those in family samples have been more positive.

Results of a high-resolution genome screen of 437 Alzheimer's disease families.

Alzheimer's disease (AD) is a devastating neurodegenerative disorder of late life with complex inheritance. Mutations in three known genes lead to the rare early-onset autosomal dominant form of AD, while a common polymorphism (epsilon 4) in the gene encoding apolipoprotein E (APOE ) is a risk factor for more typical late-onset (>60 years) AD. A recent study concluded that there are up to four additional genes with an equal or greater contribution to the disease.