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ALZHEIMER'S GENE

By Sean Henahan, Access Excellence


LOS ANGELES- A high tech combination of genetic testing and PET (positron emission tomography) scanning may help physicians recognize the early signs of Alzheimer's disease.

Researchers at the UCLA Medical School conducted the first study combining brain scans with genetic testing of patients considered at risk for Alzheimer's disease. The study enrolled 38 patients, including seven patients believed to have Alzheimer's disease. The patients also underwent psychiatric and neurological evaluations.

A recent study has shown that patients with one or two copies of the APO-E4 gene had an increased risk for Alzheimer's disease. Patients with the gene were also likely to get the disease at an earlier than average age. Patients with one copy of the gene had an average age of onset of 75 years, while those with two copies of the gene got the disease an average of seven years earlier.

All patients in the present study underwent APO-E genotyping. The APO-E gene has three allelic variants and five common genotypes. Of these, the APO-E4 allele has been associated with an increased risk for Alzheimer's disease. The type 2 allele appears to provide substantial protection against Alzheimer's disease. Another genetic abnormality, a mutation on the amyloid precursor protein gene on chromosome 21, has been linked to a more rare form of early onset Alzheimer's disease.

The patients also underwent PET scanning. This non-invasive brain scanning technique allows physicians to visualize the flow of radiolabelled glucose through the brain. This provides the clinicians with useful data on the dynamic metabolism of different parts of the brain. Most of the patient also underwent MRI (magnetic resonance imaging) scanning.

"We found that relatives who did not have dementia, but who inherited the APO-E4 gene, had lower brain function and greater right-left brain asymmetry in the parietal region than those without APO-E4, while demented patients showed the greatest changes in brain function," said Gary Small, UCLA Medical School.

MRI scans can provide detailed, high contrast pictures of the anatomy of the brain. The MRI scans showed no significant anatomic differences among those with or without the APO-E4 gene

Clinicians have long sought a way to recognize the early signs of Alzheimer's disease. By the time most people are diagnosed, the changes in the brain are well underway. The diagnosis is generally made by symptomatic presentation and specially designed patient questionnaires.

"Our findings suggest that genetic testing and brain function studies may assist in identifying people at risk for the disease. The findings are also consistent with the view that subtle changes in brain function begin gradually, years before the physician can make a clinical diagnosis," said Dr. Small.

The current findings are preliminary, and it is far too early to make comprehensive clinical conclusions based on these findings. The next step will be to conduct larger studies utilizing the same combination of PET scans, MRI scans and genetic testing, he said.

There is currently only one drug available for the treatment of Alzheimer's disease, but its use remains controversial. However, a number of interesting new compounds are in various stages of clinical trials. A method for diagnosing Alzheimer's patients still in the earliest stages of the disease would enable physicians to test some of these agents before the destruction of brain cells has progressed very far. Should one of these drugs show therapeutic promise, it would then be desirable to begin therapy as soon as the early signs of the disease were recognized.

Alzheimer's disease is the fourth leading cause of death in the developed world, after heart disease, cancer, and stroke. Alzheimer's disease costs the nation nearly $60 billion/year. The disease is named for Alois Alzheimer, the German neurologist who first described the pathology of the disease nearly 100 years ago.

Dr. Small's study appears in the March 22 issue of the Journal of the American Medical Association (3/22/95, V.273, No.12, pp. 942-947).

Transmitted: 95-03-23 18:18:37 EST


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