These results indicated that A2M-D allele was probably a weak AD protective factor, and there was a possible interaction of APOE-epsilon 4 and A2M-G alleles to increase AD risk in Mainland Han Chinese.
Through combination-analysis of the data about the A2M-I/D and the A2M-Ile1000Val variants, the A2M gene was suggested to be associated with Alzheimer's disease.
Although coding SNP (rs2230808) was confirmed to have a significant association with AD, prediction of the effects of an amino acid substitution SNP rs2230808 (R1587K) on the three-dimensional structure and function of the ABCA1 protein using PolyPhen program revealed that it is unlikely to be functionally significant.
In the present study, we examined the role of two ABCA1 polymorphisms, R219K (rs2230806) and G-17C (rs2740483) in modifying the risk of late-onset AD (LOAD) in a large American white cohort of 992 AD cases and 699 controls.
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.
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.
In either case, dysfunction of this critical toxin-elimination pathway in CJD and AD suggests that selectively increasing cerebrovascular P-gp function could open new therapeutic pathways for the prevention and/or treatment of a number of proteopathic disorders of the central nervous system.
These findings led us to hypothesize that P-gp might be involved in the clearance of Abeta in normal aging and particularly in Alzheimer's disease (AD).
These data establish a direct link between Pgp and Abeta metabolism in vivo and suggest that Pgp activity at the BBB could affect risk for developing AD as well as provide a novel diagnostic and therapeutic target.
These findings suggest that altered cholesterol metabolism and APP trafficking mediated by ABCG1 may contribute to the accelerated onset of AD neuropathology in DS.
The insertion polymorphism in angiotensin-converting enzyme gene associated with the APOE epsilon 4 allele increases the risk of late-onset Alzheimer disease.
This suggests a modest but significant increase in risk of AD and early AD pathology in women homozygous for the ACE I-allele independent of vascular factors.