The Search For Alzheimer's Disease Biomarkers

Newswise — A biomarker is a characteristic that can be measured and evaluated as an indicator of normal biological processes, pathogenetic processes, or pharmacologic responses to a therapeutic intervention. In the context of Alzheimer’s disease (AD), an AD biomarker indicates the presence or progression of the disease that may be altered by drug treatment, thereby demonstrating that it is hitting its target. Today, all clinical trials for Alzheimer’s disease utilize biomarkers of some form to assess whether the drug is actually affecting the disease in the brain.

Biomarkers measured in the cerebrospinal fluid (CSF) have been very helpful over the past 15 years in making a diagnosis as well as for predicting who will eventually develop AD. For example, CSF levels of Amyloid beta peptides are good biomarkers for the presence of amyloid plaques in the brain. Likewise, tau protein levels are useful in detecting neurodegeneration and progression of the disease. When combined, these markers are useful not only in identifying people with Alzheimer’s disease but also for predicting conversion from cognitive normalcy to very mild dementia, as well as for monitoring the rate of progression from mild cognitive impairment or very mild dementia to more severe cognitive impairment. Today we have a good idea of how they change during the evolution of the disease from pre-symptoms, mild cognitive impairment to full dementia. For this reason, some biomarkers are now part of the new diagnostic criteria for Alzheimer’s disease.

Biomarkers can be divided into two categories: 

• Imaging biomarkers: To detect Amyloid beta or tau deposits in the brain, to measure metabolic activity, and brain atrophy (or shrinkage of the brain).

• Biological biomarkers: Such as CSF or blood samples where various forms of Amyloid beta or tau protein and other compounds can be detected.

Rapid advances in the identification of Alzheimer’s disease biomarkers now more than ever make it possible to detect Alzheimer’s disease pathology in the preclinical stage of the disease in cognitively normal individuals (pre-symptomatic). There is currently great optimism that improving Alzheimer’s disease biomarkers will make it possible to select high-risk populations for clinical trials.

I am very confident that the ability to visualize in a living individual the presence of Alzheimer’s disease brain pathology (imaging biomarker), together with biological measurements (biological marker) which monitor the effects of treatment, is likely to substantially improve the development and discovery of new and more effective drugs against Alzheimer’s disease.

Domenico Praticò, MD, is the Scott Richards North Star Charitable Foundation Chair for Alzheimer’s Research, Professor and Director of the Alzheimer’s Center at Temple, and Professor of Pharmacology at the Lewis Katz School of Medicine at Temple University

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