a1 Johns Hopkins Bayview, Department of Psychiatry and Behavioral Sciences, School of Medicine, and Department of Mental Health, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, Maryland, U.S.A.
a2 Department of Mental Health, Bloomberg School of Public Health, Johns Hopkins University and Samuel Oschin Comprehensive Cancer Center, Cedars Sinai Medical Center, Los Angeles, California, U.S.A.
a3 Department of Psychiatry, Johns Hopkins Bayview and Johns Hopkins University, Baltimore, Maryland, U.S.A.
a4 Department of Mental Health, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, Maryland, U.S.A.
This synthetic review presents an approach to the use of biomarkers for the development of new treatments for Alzheimer's disease (AD). After reviewing the process of translation as applied to AD, the paper provides a general update on what is known about the biology of the disease, and highlights currently available treatments. This is followed by a discussion of future drug development for AD emphasizing the roles that biomarkers are likely to play in this process: (1) define patients who are going to progress rapidly for the purpose of trial enrichment; (2) differentiate disease and therapeutically relevant AD subtypes; (3) assess the potential activity of specific therapies in vivo or ex vivo; and (4) measure the underlying disease state, so as to (a) detect disease and assess drug response in asymptomatic patients, (b) serve as a secondary outcome measure in clinical trials of symptomatic patients, and (c) decide if further development of a treatment should be stopped if not likely to be effective. Several examples are used to illustrate each biomarker utility in the AD context.
(Received November 27 2007)
(Revised January 24 2008)
(Revised March 03 2008)
(Accepted March 05 2008)
(Online publication May 23 2008)
c1 Correspondence should be addressed to: Constantine G. Lyketsos, MD, MHS, The Elizabeth Plank Althouse Professor, Chair, Department of Psychiatry, Johns Hopkins Bayview, 5300 Alpha Commons Drive, 4th floor, Baltimore, Maryland, 21224, U.S.A. Phone: +1 410 550 0062; Fax: +1 410 550 1407. Email: email@example.com.