Brain Differences Visible In Symptomless Carriers Of Alzheimer's Gene

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Main Category: Alzheimer's / Dementia
Also Included In: Genetics;  Neurology / Neuroscience
Article Date: 29 Jul 2008 - 11:00 PDT

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Brain scans of healthy middle aged carriers of the APOE-4 gene that is known to be a risk factor for Alzheimer's Disease, showed they had brain differences that were detectable long before symptoms of the disease were likely to appear.

Dr Shi Jiang Li, professor of biophysics at the Medical College of Wisconsin in Milwaukee, US, presented the results of the study today, July 29th, at the Alzheimer's Association International Conference on Alzheimer's disease in Chicago.

Li and colleagues conducted the study at Froedtert Hospital, a teaching hospital in southeast Milwaukee, where they recruited 28 neurologically-normal people aged from 45 to 65. Twelve of them were carriers of the APOE-4 gene, while the other 16 were not. There were no significant differences in age, educational level or neuropsychological performance between the two groups.

Using functional MRI (fMRI) brain imaging, the researchers found that the APOE-4 gene carriers had significantly fewer functional connections between two important memory processing centres of the brain: the hippocampus and the posterior cingulated cortex. These parts of the brain are used in acquiring, filtering and sorting information.

Compared to the gene carriers, the non-carriers had 65 per cent more functional connectivity between the two memory processing centres.

Li said that:

"Just as if cancer could be detected when there were only a few cells, decades before it was evident, the advantage of identifying those at great risk for having Alzheimer's would be of tremendous value in development of interventional therapies."

According to the Wellcome Trust, about 15 per cent of people carry the APOE-4 gene, which causes their bodies to produce a lipoprotein called apolipoprotein (Apo) E4. Lipoproteins carry lipids (fats) in the bloodstream and are made from a combination of fat and protein.

People who have only one APOE-4 gene from one parent are three times more likely than average to develop Alzheimer's Disease. People who inherit one gene from each biological parent are ten times more likely to develop the disease.

Scientists at the Oklahoma Medical Research Foundation published a study in The Journal of Neuroscience in April last year about how they discovered the molecular mechanism that links the gene to onset of Alzheimer's. They found that ApoE4 and other apolipoproteins attach themselves to receptors on the surface of brain cells, and this allows them to piggy back onto amyloid precursor protein which then enters the cell carrying its extra burden.

Once the mass of protein is inside the cell, proteases, special enzymes that cut up proteins, attack the amyloid precursor protein mass, resulting in a mass of protein fragments that scientists believe cause cell death, memory loss, and neurological dysfunction, all symptoms that are characteristic of Alzheimer's.

What is not clear from Li's study, is whether they have found a new effect from the APOE-4 gene, or whether they have found an early pre-onset symptom of the molecular mechanism discovered by the team at the Oklahoma Medical Research Foundation.

Source: Alzheimer's Association, Wellcome Trust.

Written by: Catharine Paddock, PhD
Copyright: Medical News Today
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