Elevated levels of cholesterol play an even greater role in the development of Alzheimer's disease

APP, a protein found in several major organs including the brain is present in all people. In people with Alzheimer's, APP is abnormally processed and converted to beta amyloid protein. When fragments of this protein break off, they lead to the formation of plaques that are one of the characteristic structural abnormalities found in the brains of people with Alzheimer's disease.

'Past research has shown that high cholesterol levels appear to increase APP levels, which in turn leads to increased levels of beta amyloid protein' said Vassilios Papadopoulos, PhD, professor of cell biology and pharmacology. He added that this research showed that high cholesterol levels also increase the rate at which the amyloid beta peptides break off and form amyloid plaques.

The Georgetown research also found that high cholesterol increases the production of apolipoprotein E (APOE), which is responsible for transportation of cholesterol out of the cell. Researchers discovered that too much APOE results in the accumulation of free cholesterol, which is toxic to human nerve cells.

Papadopoulos and colleagues found that a certain type of protein, bovine lipoproteins, would bind with the free cholesterol, allowing it to be transported back to the liver and negating its harmful effects.

'By giving the dangerous free cholesterol something to bind to, we are paving the way for possible new therapies,' Papadopoulos said. 'Our study adds to the growing body of evidence implicating high cholesterol as a significant risk factor in Alzheimer's disease, and breaks new ground in showing the damage caused by excessive levels of cholesterol.'

An Alzheimer's Society statement on this news is as follows:

Cholesterol and Alzheimer's disease - where's the link?

A number of pieces of research point to a link between cholesterol and Alzheimer's disease:

• Major epidemiological studies have shown with a high degree of likelihood that people who have cholesterol levels above 6.5 in mid-life increase their risk of Alzheimer's disease in later life at least 2.5 times.
• The genetic form of the protein that is primarily responsible for transporting cholesterol in the body (apolipoprotein E) also determines an individual's risk of developing Alzheimer's disease. People who carry one copy of the E4 gene variant of apolipoprotein (ApoE4) increase their risk of Alzheimer's disease by 4 times, people with two copies of the ApoE4 gene increase their risk by 16 times.
• People who are prescribed a class of drugs called 'statins' (drugs used to lower blood cholesterol) also have a reduced risk of developing Alzheimer's disease.
• These three pieces of evidence point to a common factor - cholesterol - and implicate it as contributing cause of Alzheimer's disease.

Cholesterol and APP (amyloid precursor protein)

One of the key pathological changes in Alzheimer's disease is the accumulation of microscopic plaques of insoluble amyloid protein in the brain. These plaques are neurotoxic and cause surrounding nerve cells to die.

Amyloid protein is produced by the body from the amyloid precursor protein gene. The gene codes for a very large protein, which is then cut down to make A-beta peptide. In Alzheimer's disease the normally soluble A-beta peptides clump together forming the insoluble beta-amyloid protein - the main constituent of amyloid plaques.

The new research being presented in San Francisco appears to suggest that high levels of cholesterol cause the body to produce more APP. Because more APP is being produced, more A-beta peptide is produced, and because there is more A-beta, there is a greater chance of aggregation and plaque formation.

This appears to be a very neat theory, tying together the previous strands of research, and showing us how cholesterol is exerting its effect in Alzheimer's disease.

However, the research is test-tube based, and has to be interpreted with caution. It is also important that this research is properly published and subjected to scientific scrutiny.

This research doesn't at present point to any new treatments for Alzheimer's disease, but it does add additional weight to calls for people in mid-life to ensure that they know what their cholesterol levels are, and to seek treatment if the levels are high.