Harvard Mental Health Letter

Biomarkers for Alzheimer's disease

The brain changes that lead to Alzheimer's disease probably begin years, and possibly even more than a decade, before symptoms such as memory impairment appear. For this reason, Alzheimer's researchers have long hoped to find biomarkers — early biological signs of disease pathology — that could help identify people at risk before symptoms develop. Heart disease provides one example of how biomarkers can be useful. Elevated levels of unhealthy LDL cholesterol or total cholesterol, detected with a simple blood test, are biomarkers that indicate someone may be at increased risk of having a heart attack. Statins (anti-cholesterol drugs) reduce both LDL levels and risk of heart attack. As yet, however, there is nothing close to an Alzheimer's equivalent of a cholesterol blood test. The tests for two of the most promising categories of Alzheimer's biomarkers — brain imaging scans and spinal fluid sampling — are more cumbersome to perform than blood tests. Although the research on these biomarkers is interesting and may be promising, none are yet reliable enough to use in the clinical setting. Perhaps most significant for patients concerned about their own risk, no treatments are available to stop Alzheimer's disease progression. Although a number of "disease-modifying" compounds are under investigation, so far all have failed in the late-stage clinical trials that are necessary to prove efficacy. The most recent flop occurred in August 2010, when a drug company halted development of a compound known as semagacestat after patients with Alzheimer's participating in a clinical trial fared worse after taking the drug than those taking placebo. Still, the research on biomarkers continues because some investigators believe that the disease-modifying drugs must be given earlier in the Alzheimer's disease process to be effective. Whether or not that is true remains to be seen.
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