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Dementia, cholesterol and the soft science of dietary fat
- Alexei R Koudinov, Natalia V Koudinova (27 July 2001)
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Alexei R Koudinov, visiting scientist Department of Biological Regulation, Weizmann Institute of Science, Rehovot 76100, Israel, Natalia V Koudinova
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To add to the discussion about how statins can help prevent dementia
( BMJ 2000;321:1241
) we would like to bring readers attention to the recent Science magazine
New Focus article “The Soft Science of Dietary Fat” (1).
The dramatic saga left no space for the neurology of low-fat no-cholesterol eating that become the concept of healthy food in industrialized countries during the past 30 years. We have to admit that except of few undercited publications (2) the question of how dietary fat modulation and its biological compensation affects brain lipid chemistry, learning and memory remains non-addressed. This question, however, is becoming important nowadays when an increasing number of papers implicate cholesterol in Alzheimer’s disease. Of these papers our own recent contribution provided experimental evidence that cholesterol is essential for proper synaptic function and neuronal degeneration (3). Thus, neuronal cholesterol homeostasis failure is causative for Alzheimer’s marker of excessive PHF-tau phosphorylation and is sufficient to induce neurotransmission and synaptic plasticity impairment (3). Chronic defect of brain cholesterol homeostasis is also essential for impairment of beta amyloid neurochemistry, as corroborated by amyloid pathology in the brain of rabbits and mutant human amyloid precursor protein transgenic mice fed cholesterol diet, as well as in cholesterol-fed rats also expressing increased cholesterol synthesis and synaptic dysfunction in the hippocampus (see Ref. 3 for details). Shown to specifically correct brain cholesterol (4), statins likely exert their protective effect primarily by correcting neuronal cholesterol and secondarily by slowing (or reversing) tau and amyloid pathology. It is documented that brain cholesterol is a delicate substance very sensitive to many influences, ranging from lipid preparation diets and chemical delivery systems for drugs and food additives to learning process itself (2, 3). Further understanding functional biochemistry of brain cholesterol, unraveling neurobiological effects of the antifat lifestyle and its relation to the increase in dementia and Alzheimer’s disease prevalence during 1970s and 1980s (5) became an obstacle of neurodegeneration understanding. It would be a shock to learn that physician “no harm” key rule hardly fits the neurobiological principles of the low fat eating. The statin clinical data and our report on the role of cholesterol in synaptic plasticity and neurodegeneration emphasize the need of concentrating efforts on cholesterol front of Alzheimer’s battle in addition to yet failed to bring AD cure 15-years-long amyloid odyssey. References:
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