Cutting cholesterol levels may protect against Alzheimer's
and stroke but it may also help ward off Alzheimer's disease,
according to new research.
Tobias Hartmann and colleagues from the University of Heidelberg in Germany will reveal in the November issue of Nature Cell Biology (DOI: 10.1038/ncb1313) how a mysterious protein affects Alzheimer's disease and its link to cholesterol.
Their work builds on earlier evidence showing a significant role played by dietary fats in Alzheimer's disease.
It could add further market potential to foods designed to lower cholesterol, already seeing strong demand from consumers looking to lower their risk of heart disease.
Although heart disease is the biggest killer globally, the cause of Alzheimer's, which currently affects an estimated 12 million around the world, is still not properly understood yet it is expected to increase substantially along with the rising numbers of elderly.
A number of studies suggest that fish consumption can protect against the disease - perhaps owing to the omega-3 fats found in some kinds - while saturated fat and high dietary cholesterol intake has been associated with an increased risk of cognitive decline.
Hartmann's paper offers a potential explanation for this link to cholesterol levels.
The authors note 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 the disease.
Produced in normal cells, the protein 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.
The German researchers examined whether APP and AB could affect lipid metabolism by testing cells derived from mice engineered to remove expression of the enzymes that generate AB. They had higher levels of cholesterol and 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 APP does impact on lipid metabolism. The study also suggests 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.
The findings suggest a clear benefit from controlling lipid intake through the diet.
