Department of Neuropsychiatry and Behavioral Sciences
Alzheimer's DNA Bank » Annual Report
DIRECTOR: DR. Randolph B. Schiffer
JANUARY, 2000
As we enter the new millennium, we are pleased to state that the DNA Bank continues to grow and the research becomes more exciting. The DNA Bank started in November of 1993 with funding from the State of Texas. It currently has enrolled over 2,400 families of patients with memory problems and over 9,500 family members. To enroll into the DNA Bank, family members fill out paper work and then have their blood drawn. That is, family members complete a detailed medical and family history form on the patient. As we want the medical records on the patients, the spouse or person having power of attorney for the patient signs medical release forms for physicians and hospitals. Family members who are participating also fill out a short form of identification and sign consent forms indicating that they understand the study. We draw two tubes of blood from family members (three tubes from the patient). Family members who live out of town can enroll by mail. We send tubes and forms to those requesting them. Once the blood is drawn, the samples are returned to us by overnight mail. We receive samples from family members who live all over the country.
The staff from the DNA Bank has traveled to 87 towns and cities in Texas and
visited over 150 sites to enroll families. The sites are the homes of local
support groups, nursing facilities, senior citizens centers, churches, or
schools. Our visits have been the subject of local newspaper articles and TV
shows. We also attend family reunions as many family members can enroll at one
time.
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Families who enroll into the DNA Bank receive our newsletter, the DNA Update, which describes our research as well as new findings from around the world. Our mailing list is over 5000. There are also 25 copies of our third video in circulation that discusses Alzheimer's disease and also describes our research. We encourage family members to call us with questions at 1-800-661-0968. Copies of our newsletters and manuscripts are at our web site www.ttuhsc.edu/som/Neuropsychiatry/dnabank/. We have continued our support group in Lubbock that meets the first Thursday of the month.
The DNA Bank is part of the Alzheimer's autopsy network and services the families enrolled. Even today the only way to confirm the diagnosis of Alzheimer's disease is by autopsy. We contract with the neuropathologists (Dr. R. Leech and Dr. R. Brumback)in Oklahoma for the pathology. We have had 137 autopsies that were definite Alzheimer's disease thus far.
Dr. J. Schwankhaus, our consultant neurologist, reads the medical records on
the patients to determine the clinical diagnosis. For the diagnosis of probable
Alzheimer's disease, we use the criteria established by NIH-ADRDA. This includes
a progressive decline in cognition and appropriate blood work to rule out other
medical conditions. We also include a CT scan or MRI of the brain which may show
cortical atrophy but no evidence of strokes or tumors. We have confirmed the
diagnosis of probable Alzheimer's disease on 492 patients thus far. Of these,
116 have early-onset disease with symptoms starting before the age of 65 years
while 377 have late-onset disease. There are 100 patients with possible
Alzheimer's disease, meaning the patient is still in the very early stages. We
are waiting for additional medical records on the remainder. We also have over
200 Parkinson's patients and over 100 Multiple Sclerosis patients enrolled, as
well as several patients with amyotrophic lateral sclerosis, Down's syndrome,
and Huntington's disease. We encourage spouses to enroll as they serve as
controls for the genetic studies; at the present time there are almost 1500
spouses enrolled.
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Currently mutations in six genes have been linked with Alzheimer's disease. These include mutations in the gene for the beta amyloid protein on chromosome 21, mutations for the two presenilin proteins on chromosomes 14 and 1, and the risk factors APOE 4 and APOCI A on chromosome 19 and alpha-2 macroglobulin on chromosome 12. About 40% of our Alzheimer's patients have the APOE 4 allele. We were the first to identify that the APOCI A allele is also present in 40% of the Alzheimer's patients. We found that the presence of these two risk factors is significant for the disease. These two genes are very close together on chromosome 19. We are examining the area surrounding these two genes for additional markers linked with the disease. We also examined the mutations found in the gene for alpha-2 macroglobulin in our patients. We did not find an increased frequency of the mutations when compared with control spouses. We did find that there were markers downstream from this gene that may be linked with the disease. We are examining this area of chromosome 12 as well.
In collaboration with Dr. E. Drigalenko in our group, we did a complicated
mathematical analysis of our patients to determine whether there are indeed
mutations in genes linked with late-onset Alzheimer's disease. We found that
patients with age of onset of symptoms between 65 and 75 years have a recessive
inheritance; patients with age of onset ?75 years have a dominant inheritance.
This is the first time that anyone has been able to prove that there are
mutations in genes linked with late-onset disease.
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We have also found that a particular form of late-onset Alzheimer's disease may be linked with markers on chromosome 3. In this study the patient had the typical clinical signs of the disease. However, at autopsy the brain only had plaques but no tangles (the characteristics of an Alzheimer's brain). We believe that this may be a milder form of the disease. We are searching for the gene that may be the cause of this milder form of the disease.
We have been very busy these past five years. Now that we have a good base in
the DNA Bank, our genetic studies have become quite significant. We are excited
by our findings this past year and hope to find some of the genes linked with
late-onset Alzheimer's disease soon. We do appreciate the fantastic response
from the families here in Texas that have enrolled into the DNA Bank and for
their courteous response to our questions on medical and family histories. The
more families that we have enrolled into the DNA Bank, the better our chances
are of finding the genes causing this dreaded disease.
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