Methylation of 2 of 36 CpG islands in ABCA2 gene with high diagnostic accuracy of AD from controls in ROC analyses were found to be negatively associated with AD risk in univariate analysis.
Our results showed that A2M V1000I polymorphism in German, Korean, Chinese, Spanish, Italian and Polish populations, rs90883 of ABCA2 gene in French, American, Swiss, Greek and Japanese populations, 2384G >A of CHAT gene in British and Korean populations and LPL Ser447Ter in the Northern-American population were associated with the risk of AD.
It is important to study the role of ABCA2 in regulating cholesterol homeostasis in neuronal-type cells because ABCA2 has been identified as a possible genetic risk factor for Alzheimer's disease.
This report identifies ABCA2 as a key regulator of endogenous APP expression and processing and suggests a possible biochemical mechanism linking ABCA2 expression, APP processing and Alzheimer's disease.
These studies have implicated ABCA2 as a therapeutic target in modulating the drug resistance phenotype prevalent in human cancers and in the treatment of neuropathies, including Alzheimer's disease and myelin-related disorders.
These data suggest that ABCA2 may exert population-dependent effects on the genetic risk for sporadic AD and support a role of ABC lipid transporters in the pathogenesis of this disease.
The ABCA2 transfected cell line expressed resistance to a free radical initiator, confirming involvement in protection against reactive oxygen species and suggesting a further possible link to AD.