Alzheimer's Disease - Understanding The Lipid Connection

Studies suggest that high cholesterol levels can be linked with increasing levels of a protein called amyloid-beta (AB). Accumulation of this protein is a central feature of Alzheimer's and thought to lead to the neuronal dysfunction and death associated with Alzheimer's. Produced in normal cells, AB comes from a larger protein called amyloid precursor protein (APP). The normal function of both remains a mystery but AB's levels increase sharply in Alzheimer's.

Tobias Hartmann and colleagues examined whether APP and AB could affect lipid metabolism. Cells derived from mice, engineered to remove expression of the enzymes that generate AB had higher levels of cholesterol and of another lipid called sphingomyelin. The team pinpointed these effects to altered activities of two key enzymes in the metabolic pathways of these lipids. They also restored normal levels of these lipids and the enzyme activities by treating these cells with AB. The authors concluded that one function of normal APP is in lipid metabolism - a surprising finding. This study also suggest the existence of a loop - AB levels are controlled by lipids and lipids, in turn, control AB levels - so, such a spiralling mechanism could result in the abnormally high AB levels seen in Alzheimer's, having clear consequences for designing therapeutic interventions.

Author contact:

Tobias Hartmann (University of Heidelberg, Germany)
E-mail: tobias.hartmann@zmbh.uni-heidelberg.de

bstract available online.

(C) Nature Cell Biology press release.

Message posted by: Trevor M. D'Souza