Cholesterol-Lowering Drugs and Alzheimer’s Disease

It has been widely reported that drugs that lower cholesterol may slow the progression of Alzheimer’s disease. The role of cholesterol in Alzheimer’s disease is attracting increasing attention from researchers and there are conflicting messages coming form a great deal of reports.

Despite the fact that wide-spread opinion about high levels of cholesterol still remains negative, there is a growing body of evidence suggesting its beneficial role in the brain.

This is supported by a study showing that high cholesterol blood levels correlate with a lower death rate index and a better outcome following a first stroke. (Neurology 2000, 54:1944-1948).

There was also a positive relationship between a high cholesterol diet and improved preservation of cognitive functions in rats which previously underwent an oxygen deficiency period. (Physiol Behav 2004, 82:703-711).

Recent findings reported a flow of peripheral cholesterol through the blood-brain barrier in the form of 27-hydroxycholesterol, a potent regulator of several cholesterol-sensitive genes. (J Lipid Res 2005, 46:1047-1052).

It has also been found that patients suffering from AD have lower levels of cholesterol in cerebrospinal fluid (the brain and spinal cord). (J Lipid Res 2000, 41:963-974).

The importance of cholesterol in the functioning of the brain is reflected by the fact that the human brain, making up only 2% of total body weight, contains as much as 25% of the total cholesterol pool. (Curr Opin Lipidol 2001, 12:105-112).

The above is extracted from “Does cholesterol act as a protector of cholinergic projections in Alzheimer’s disease?”. The researcher goes on to present his hypothesis, which is of a technical nature and not easily explained in laymans terms, and concludes:

If the hypothesis is proved to be true it should first of all change the negative attitude towards blood high cholesterol levels in clinical practice. In particular the use of statin drugs in older subjects with neurological disorders should be revised.

Recently there is an increasing number of reports indicating uncertainties related to this issue. However this should be handled with care, since some authors even acknowledging the positive role of cholesterol in the brain do not exclude some beneficial actions of this group of drugs.

Nevertheless, if the hypothesis is validated it may result in changes in some diet recommendations, especially considering that definitely not all cases of high blood cholesterol must result in arteriosclerosis.

This is supported by findings indicating homocysteine and not cholesterol as the primary vessel damaging factor in this disease. (Mil Med 2004, 169:325-329).

Moreover it would open up new alleys in brain function studies in general and Alzheimer’s disease in particular.

It would imply the need of widening our understanding of the activity of cholesterol in the plasmalemma of neurons and mechanisms by which cholinergic receptors interact with plasmalemmal cholesterol.

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Bohr IJ. Does cholesterol act as a protector of cholinergic projections in Alzheimer’s disease? Lipids in Health and Disease 2005, 4:13doi:10.1186/1476-511X-4-13. © 2005 Bohr; licensee BioMed Central Ltd.
This is an Open Access article distributed under the terms of the Creative Commons Attribution License (

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