Determining Alzheimer’s Before Symptoms Appear
Currently, the diagnosis and medical management of Alzheimer’s disease begins after a gradual decline in mental acuity. Researchers now believe early markers indicating the development of the disease may be detected in high risk individuals possibly decades before symptoms appear.
The report, published in the July issue of Archives of Neurology, suggests the presence of lower than normal levels of particular proteins in the cerebrospinal fluid represent the beginning formation of brain plaques characteristic of Alzheimer’s.
According to background information in the article, 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). 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 â-amyloids, begin forming years before affected individuals experience any symptoms of the disease. As â-amyloid proteins, predominately of a type known as Aâ42, clump together, fewer are available to circulate through the nervous system. Therefore, lower levels of the Aâ42 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 Aâ42 and another â-amyloid, Aâ40, 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’ Aâ42 and Aâ40 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 Aâ42. For those who did not have the APOE*4 allele, Aâ42 levels rose slightly until about age 50 years then begin to decline slowly. On the other hand, those with the APOE*4 allele experienced a slight decline in Aâ42 in their younger years and then a dramatic drop between ages 50 and 60 years. Levels of Aâ42 were not associated with scores on any cognitive or memory tests.
“In persons with the APOE*4 allele, decline in cerebrospinal fluid Aâ42 concentration possibly begins in young adulthood, followed by marked acceleration of this decline beginning in midlife–decades before clinical manifestations of Alzheimer’s disease,” the authors write. The same relationship did not hold true for Aâ40, which, although it is also found in amyloid plaques, is less prevalent there than Aâ42; levels of Aâ40 did not change with age in those with the APOE*4 allele and decreased with age in those without the APOE*4 allele.
“These findings have implications for the preclinical diagnosis of Alzheimer’s disease, as well as for treatment,” the authors conclude. “Therapeutic strategies aimed at prevention of Alzheimer’s disease may need to be applied in early midlife or even younger ages to have maximal effect on amyloid deposition. Primary prevention trials for Alzheimer’s disease targeting elderly persons may be too late to affect the early stages of disease pathology.”
Source: JAMA and Archives Journals
Nauert PhD, R. (2015). Determining Alzheimer’s Before Symptoms Appear. Psych Central. Retrieved on March 21, 2018, from https://psychcentral.com/news/2006/07/11/determining-alzheimers-before-symptoms-appear/83.html