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 A42, the average level for the first-degree relatives is about 1.21.3 times that of non-relatives, and for A40, 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.
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