Translational Approaches in Alzheimer’s Disease
2016
The identification of potential diagnostic, pharmacodynamic, and patient selection biomarkers has had a profound impact on Alzheimer disease (AD) drug development. These biomarkers include amyloid positron emission tomography imaging and the measurement of amyloid beta in the cerebrospinal fluid. Amyloid-targeting agents can be loosely categorized into three categories: (1) agents that are designed to prevent the aggregation and formation of amyloid plaques, (2) agents that are designed to stimulate the innate immune system to clear existing amyloid plaques and prevent further deposition, and (3) agents that prevent the formation of the precursor of amyloid, the Aβ peptide. Biomarkers have been instrumental in determining the disease-modifying effects of these treatments and thus ultimately have an impact on whether drugs continue in development all the way to approval or are instead terminated. Furthermore, the use of newly developed biomarkers has had a profound impact on the diagnosis of this disorder. This chapter reviews the role of amyloid in AD and shows examples of translational biomarker strategies used in drug development for antiamyloid therapeutic agents.
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