Chicago Early signs of the development of Alzheimer's disease can be seen in the cerebrospinal fluid of middle-aged adults who are genetically predisposed to the neurologic condition, according to a report in the July issue of Archives of Neurology, one of the JAMA/Archives journals.

The two strongest risk factors for Alzheimer's disease are aging and the presence of an allele (type of gene) known as apolipoprotein E*4 (APOE*4), according to background information in the article. Those with the APOE*4 allele develop clinical dementia about 10 to 15 years earlier than those who do not have the APOE*4 allele. Previous studies have shown that the plaques that form in the brain during Alzheimer's disease, which are made of proteins known as -amyloids, begin forming years before affected individuals experience any symptoms of the disease. As -amyloid proteins, predominately of a type known as A42, clump together, fewer are available to circulate through the nervous system. Therefore, lower levels of the A42 in the cerebrospinal fluid surrounding the brain and spinal cord serve as biomarkers or chemical indicators of the development of Alzheimer's disease.

Elaine R. Peskind, M.D., VA Puget Sound Health Care System and University of Washington School of Medicine, Seattle, and colleagues estimated the combined effect of aging and the APOE*4 allele on levels of A42 and another -amyloid, A40, in 184 adults (94 men and 90 women, average age 50 years). The participants underwent clinical and laboratory screening and were found to be cognitively normal--that is, they had no difficulties with thinking, learning or memory. Researchers took samples of cerebrospinal fluid in the morning after an overnight fast and measured participants' A42 and A40 levels in addition to determining whether each individual had the APOE*4 allele.

Those who were older and who had the APOE*4 allele were more likely to have lower levels of A42. For those who did n
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Contact: Jeri Rowe
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JAMA and Archives Journals
10-Jul-2006