Cholesterol
en de ziekte van Alzheimer.*
Uit
dit onderzoek blijkt dat hoge cholesterol waarden mogelijk ook het risico op
Alzheimer vergroten.
Alzheimer's
disease - understanding the lipid connection
Keeping an eye on cholesterol can reduce the risk of
heart disease and stroke but new research shows how it may also have benefits
for warding off Alzheimer's disease. The function of a mysterious protein, how
it affects Alzheimer's and its link to cholesterol is reported in the November
issue of the Nature Cell Biology.
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.
NATURE CELL BIOLOGY (Okt. 2005)