Major biomarker candidates for Alzheimer's disease explored

Mar 8 2006

Alzheimer's disease - specific biomarkers clearly are needed for the differential diagnosis of cognitive impairment in the elderly.

What sets age-related disorders like hypertension, hypercholesterolemia and diabetes mellitus apart from Alzheimer's disease is that each has biomarkers that can be followed easily and repeatedly, not simply to diagnose, but also to monitor response and optimize treatment. In contrast, the current role of clinical laboratory evaluation for dementia is exclusionary. The development of such biomarkers is critical to translating efficiently the new therapeutic approaches for AD under development by many research groups into treatments for the millions who suffer from AD.

The March issue of the Journal of Alzheimer’s Disease published by IOS Press is devoted to the current research into "Biomarkers for Alzheimer’s Disease.” In the foreword by Elaine R. Peskind and guest editor Thomas J. Montine (University of Washington), the challenges and limitations of our current knowledge of AD biomarkers are outlined. These investigators emphasize that "Progress toward controlling if not eradicating AD is at a crossroads where clinical, pathological and basic science studies have identified therapeutic targets that are now being tested. Critical to translating this knowledge to improved patient care will be developing panels of biomarkers that complement the clinical exam, cognitive testing, and neuroimaging." In six articles, prominent researchers and clinicians involved in AD studies review the search for potential biomarkers for this debilitating disease.

Jeffrey L. Cummings (University of California at Los Angeles) discusses the use of clinical evaluation as a biomarker for AD, pointing out the need for biomarkers that accurately reflect clinical outcomes.

Following this theme, Douglas Galasko (University of California at San Diego) reviews some of the current candidates for AD biomarkers, such as amyloid-beta, tau, and phospho-tau. Other biomarkers that target inflammatory and oxidative damage processes may have future potential.

In a disease with no known cure and no treatments that can delay onset or prevent progression, prediction of future pathology is particularly important. In “The search for antecedent biomarkers of Alzheimer’s disease,” Anne M. Fagan, Cynthia A. Csernansky, John C. Morris, and David M. Holtzman (Washington University in St. Louis), discuss some of the challenges surrounding the development of biomarkers for “preclinical AD.”

Thomas J. Montine, Joseph F. Quinn, Kathleen S. Montine, Jeffrey A. Kaye, and John C.S. Breitner (University of Washington and Oregon Health & Science University), in “Quantitative in vivo biomarkers of oxidative damage and their application to the diagnosis and management of Alzheimer’s disease,” discuss how the monitoring of F2-isoprostanes in cerebro-spinal fluid (CSF) is showing promise as a diagnostic tool for monitoring potential anti-oxidant therapies for AD.

Inflammatory processes have also been implicated in AD. Robert E. Mrak and W. Sue T. Griffin (University of Arkansas) review proinflammatory cytokines as potential markers for AD, pointing out in “Inflammatory biomarkers in Alzheimer’s disease” the difficulties in the use of such markers due to complicating genetic factors.

Finally, Jing Zhang, David R. Goodlett, and Thomas J. Montine (University of Washington) discuss recent advances in genomics, proteomics, and metabolomics. In “Proteomic Biomarker Discovery in Cerebrospinal Fluid for Neurodegenerative Diseases,” the prospect for clinical diagnosis via unique protein markers is reviewed, as well as the practical limitations of proteomic analysis of human CSF.

In addition to the articles, the issue features transcripts of two live panel discussions of the Alzheimer Research Forum, “Imaging in Alzheimer's Disease: The Current State of Affairs” and “Making a BioMark on Alzheimer Disease.” (The Alzheimer Research Forum, founded in 1996, is the web's most dynamic scientific community dedicated to understanding Alzheimer's disease and related disorders.)