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Evidence found for genes that affect risk of developing Alzheimer's disease
Date:1/17/2008

16 participants in the federally-funded Mayo Clinic Study of Aging, who served as their comparison group. None of the study participants have been diagnosed with AD. They selected younger first-degree relatives and controls (age 20-65) to study so as to minimize the effect of age on A levels, and they also tested participants for their APOE variant. In a series of sub-studies in control groups, the investigators confirmed that blood A levels stayed consistent over a period of weeks, and that both A40 and A42 levels rise significantly in people over age 65 who do not have dementia.

In the young, cognitively normal first-degree relatives of LOAD patients, they found that levels of both A40 and A42 in the blood were significantly elevated, compared to their spouses (which served as the control group). Studying the other group of 103 first-degree relatives of AD patients, the researchers also found significantly higher levels of A42.

Overall, comparing first-degree relatives with non-relatives, they found that for A42, the average level for the first-degree relatives is about 1.21.3 times that of non-relatives, and for A40, it was 1.11.4 times greater. Just like measuring cholesterol in the blood, the absolute magnitude of such an increase does not have to be large in order to be worrisome, Dr. Ertekin-Taner says.

They then determined that this rise in A is not due to the APOE4 gene. On the contrary, the plasma A levels of relatives with the APOE4 gene variant were lower significantly so for A42 than the levels of those who lacked the gene. This means two things, says co-author Steven Younkin, M.D., Ph.D.: that genetic factors other than the ones already known must lead to plasma A elevations in first-degree LOAD relatives, and that there is a strong mechanistic interaction between APOE4 and A leading to increased deposition of A in the brain and hence lower plasma A levels in these subjects.'/>"/>

Contact: Cynthia Nelson
nelson.cynthia1@mayo.edu
904-953-0464
Mayo Clinic
Source:Eurekalert

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