The vast majority of Alzheimer's disease cases are likely to be inherited in a complex manner involving multiple genes and environmental factors that modify genetic risk. As the risk associated with the e4 allele of APOE only accounts for approximately 50% of complex cases, other causative genes remain to be identified. Strong evidence indicates that at least one additional risk gene exists on chromosome 12.
We investigated the possible association of four genes in a large case-control study (n>1200). We described associations between AD and several polymorphisms of LRP (LDL receptor related protein), LBP1/CP2/LSF (Lymphocyte stimulating factor) and OLR1 (oxidized LDL-receptor 1) genes, but not with A2 macroglobulin polymorphisms. These data tend to indicate that several genes on this chromosome may act as susceptibility gene for AD and suggest that both inflammation and cholesterol metabolism play an important role in the development of the disease.
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