Understanding the link between cholesterol and risk of AD

Nan Wang, PhD
Columbia University (New York, NY)
Year Awarded:
2007
Grant Duration:
April 1, 2007 to March 31, 2009
Disease:
Alzheimer's Disease
Award Amount:
$150,000
Grant Reference ID:
A2007368
Award Type:
Pilot
Award Region:
US Northeastern
Partial funding for this award was made possible through the generosity of the Kenneth and Ann Reim Trust Fund

Role of ABCG1 and ABCG4 in Abeta Generation in Brain

Summary

This research seeks to understand the role of cholesterol transporters in the production of Amyloid Beta

Details

Recent studies suggest that cholesterol balance in the brain may affect development of Alzheimer's disease. Increased cholesterol is associated with increased risk of Alzheimer's disease while decreased cholesterol appears to reduce it. Recently, we have identified two membrane transporters that are involved in cholesterol transport in cells. These transporters are highly expressed in the brain. Now we have evidence suggesting that increased activity of these transporters enhances generation of Abeta, the molecule aberrant elevation and deposition of which is considered to be the major cause of Alzheimer's disease. Importantly, deficiency of the transporters appears to decrease Abeta production in the brain. ABCG4, one of two transporters, is mainly expressed in the brain and studies with mouse models of ABCG4 deficiency suggest that ABCG4 deficiency does not affect animal development and no impaired physiological functions have been identified in these mice. Therefore, ABCG4 may represent a novel drug target for treatment of Alzheimer's disease.

Publications

Wang, N., Yvan-Charvet, L., Lutjohann, D., Mulder, M., Vanmierlo, T., Kim, T.W. and Tall, A.R. (2008) ATP-binding cassette transporters G1 and G4 mediate cholesterol and desmosterol efflux to HDL and regulate sterol accumulation in the brain. FASEB J. 22(4):1073-1082.  

Tansley, G.H., Burgess, B.L., Bryan, M.T., Su, Y., Hirsch-Reinshagen, V., Pearce, J., Chan, J.Y., Wilkinson, A., Evans, J., Naus, K.E., McIsaac, S., Bromley, K., Song, W., Yang, H.C., Wang, N., DeMattos, R.B. and Wellington, C.L. (2007) The cholesterol transporter ABCG1 modulates the subcellular distribution and proteolytic processing of b-amyloid precursor protein. J Lipid Res. 48(5):1022-1034.  

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