Alzheimer's disease is the most common neurodegenerative cause of dementia in the elderly population that involves a breakdown of normal brain cells. It affects 25 million people worldwide and is the 4th leading cause of death in industrialized nations like the US. Sadly this disease is only increasing as our population including the baby boomers continues to age. In fact, the number of people with Alzheimer's disease is expected to double every 20 years! From a brain tissue perspective, the hallmark of this disease is the development of plaques made of a protein called amyloid that replaces normal brain tissue. This leads to the progressive and irreversible loss of memory, function, and rational thinking. This progressive dementia is therefore progressively fatal.
What is the link between cholesterol and Alzheimer's disease? Firstly, the formation of these abnormal amyloid proteins involve parts of the brain cell membranes which are very rich in lipid and cholesterol. And, secondly, the brain is the most cholesterol rich organ in our bodies, even more so than the liver, which is the main cholesterol producing organ. The brain contains about 25% of our total body cholesterol despite the fact that is only 2% of our body weight. Cholesterol is a key ingredient for normal brain cell function and for maintenance of normal brain cell signal trafficking.
Early population studies suggested that high serum cholesterol is a risk factor for the development of early Alzheimer's disease. In particular, if a person carries a certain type of lipoprotein (remember that cholesterol and lipids are carried in our blood in packets that contain apoproteins and that apoproteins+lipids = lipoprotein) called ApoEε4, then the mean age of onset of Alzheimer's decreases from 84 years old to 68 years old. Having this ApoEε4 is also associated with high cholesterol and increased heart disease risk. If you have a different or more normal form of ApoEε, your risk of dementia and heart disease is not increased. Clearly, genetics are the major determinant of which form of ApoEε you are going to have. Animal laboratory research has also confirmed that high serum cholesterol seems to promote earlier development of these amyloid plaques in the brain.
Given the above observations, people began to wonder if lowering serum cholesterol would protect against the development of Alzheimer's disease. Early retrospective observational studies seemed to support this hypothesis. From the late 1990s to early 2000, 5 out of 6 of these observational studies concluded that the use of a statin drug to lower serum cholesterol was associated with a reduced risk of Alzheimer's disease.
Unfortunately, this initial enthusiasm for the use of statins has faded. Retrospective studies are not as powerful and reliable as prospective and randomized ones. Since early 2000, at least 4 randomized trials and prospective observational studies have found no clear association from statin use and the development of Alzheimer's disease. Again we are reminded that initial observations must be proven to be true through well designed scientific studies before they change patient management. Furthermore, the pendulum of using statin drugs in improving mental function has now swung from positive to negative. I recently wrote an article in which scientists were concerned that statins may now cause a decline in mental function and memory. (see my article entitled "Do Statins Lower Your IQ?")
Although cholesterol plays a role in the development of Alzheimer's disease, it is unclear if there is any relationship to blood serum cholesterol as opposed to brain cholesterol. Chemically the same cholesterol, brain cholesterol appears to be independent and unaffected by serum cholesterol levels. One reason is that the brain has a very tightly regulated barrier that controls what the brain gives and receives from our blood stream. It seems that serum cholesterol is impermeable to this blood brain barrier. Furthermore, brain cholesterol is largely produced by the brain itself and not from the liver or from our diet. And, lastly, brain cholesterol turnover is quite slow - on average half the brain cholesterol is replaced in ~5yrs. These may be some reason as to why statins do not seem to affect Alzheimer's disease.
Our understanding of the role of cholesterol and Alzheimer's disease is incomplete at best. Brain cholesterol does play a role in Alzheimer's disease but whether serum cholesterol is a factor is not clear. And today's evidence does not seem to support a role for the use of statin or other cholesterol lowering medications in the treatment of this disease.
Published On: August 05, 2008