Early Warning: Detecting Alzheimer’s in the Blood and Brain Before Memory Loss

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Alzheimer’s doesn’t happen suddenly, but scientists are still struggling to find the best ways of capturing the first signs of trouble.

In two separate studies, researchers report some success in looking for telltale markers in the blood and spinal fluid that could signal the beginning of Alzheimer’s.

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In one report published in the journal Neurology, scientists studied cerebrospinal fluid of 265 middle-age participants collected for the Biomarkers for Older Controls at Risk for Dementia (BIOCARD) project between 1995 to 2005. About 75% of the participants had a close family member that had Alzheimer’s disease, which put the volunteers at higher risk for developing the disease. Each year, the participants performed physical and neurological tests to track their performance.

During this time, two proteins,  phosphorylated tau and beta amyloid in the spinal fluid, changed significantly. Both are associated with Alzheimer’s — experts currently believe that amyloid plaques build up to suffocate brain neurons, and that the debris of dying nerve cells triggers the formation of tau tangles, made up of inflammatory factors and nerve fibers. By matching  the changes in these proteins to the participants’ performance on cognitive and physical tests, the scientific team determined that even at the start of the study, the ratio between tau and amyloid predicted mild cognitive decline five years before noticeable changes in memory occurred. They were even able to understand how changing levels of these proteins over several years correlated with progression of the disease. Those with more tau protein than amyloid in their spinal fluid, for example, were more likely to develop symptoms of Alzheimer’s disease, and the more quickly the ratio of tau to amyloid increased, the sooner symptoms of memory loss occurred.

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Because Alzheimer’s is characterized by the deposition of amyloid plaques in the brain, the results support the idea that as the disease progresses, less amyloid is released into the spinal fluid, and more remains in the brain, where it compromises nerve function. Detecting when these plaques and tangles start to form may be critical in controlling, and eventually curing Alzheimer’s, since current drugs, which are started once memory loss occurs, may be used too late. By intervening earlier in patients who are still cognitively sound but actually in the first stages of the neurodegenerative disease, these medications may become more effective.

The researchers, based at Johns Hopkins University School of Medicine, don’t believe that their spinal fluid-based test is ready yet for identifying patients in the clinic. But it could be part of a package of tests that identify those who are vulnerable to Alzheimer’s from those who are not.

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One of those additional tests might involve the amount of atherosclerotic plaques that people have in other blood vessels in the body. Reporting in the same issue of Neurology, researchers at the University of Pittsburgh found that among a group of 91 people with an average age of 87 and no signs of dementia, those with more hardening of the arteries were more likely to have amyloid plaques in the brain. While the volunteers were not followed long enough to determine if they went on to develop Alzheimer’s, amyloid buildup is a strong indicator of the disease. “Compared to people who had low amounts of amyloid plaques and brain lesions, each unit of increase in arterial stiffness was associated with a two- to four-fold increase in the odds of having both amyloid plaques and a high amount of brain lesions,” said Timothy Hughes, the lead author of the study.

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Taken together, the two studies provide encouraging evidence that it may be possible to detect Alzheimer’s early, at a time when intervening with nerve-saving medications may be more effective. Already, new guidelines released by the Alzheimer’s Association and the National Institute on Aging in 2011 recommend that scientists adopt blood-based and spinal fluid-based tests to look for Alzheimer’s earlier — at least in research studies so these methods can be validated for use in the clinic. With more groups testing these strategies for early detection, hopefully it won’t be long before they become a part of routine care for identifying Alzheimer’s patients as early in their disease as possible.