Alzheimer’s disease prevention – The emerging role of lipids and diet

Abstract

Although Alzheimer’s disease (AD) causes massive and irreversible neurodegeneration, prevention and curing early stages of the disease appears to represent a realistic goal to be achieved in future. In fact, one of the very first effective treatments available could be derived from ordinary food sources.Overproduction of the amyloidogenic peptide Aβ42 causes AD. Thus far two physiological regulatory cycles were identified in which Aβ peptides play a major role. These regulatory cycles are involved in cholesterol and sphingolipid homeostasis. Moreover, Aβ production is under physiological conditions tightly regulated and its production rate is highly sensitive to alterations of the cellular membrane composition. Several lipids, sterols and fatty acids have thus far been identified to affect Aβ production. Most knowledge thus far has been gathered about those lipids which are themselves are target of Aβ mediated lipid homeostasis, cholesterol and sphingomyelin. E.g. cholesterol strongly increases Aβ production and cholesterol lowering with statins is a matter of intense clinical research not only for cardiovascular disease preventions but now also for AD therapy. Special interest received n-3 polyunsaturated fatty acids, especially DHA, because of their Aβ lowering effect in combination with favorable pharmacokinetics and neuroprotective properties.