By Sean Henahan, Access Excellence
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
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
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
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