Table of Contents
Advances in Geriatrics
Volume 2014, Article ID 302712, 14 pages
Review Article

CSF Biomarkers of Alzheimer’s Disease: Impact on Disease Concept, Diagnosis, and Clinical Trial Design

Department of Neurology, Knight Alzheimer’s Disease Research Center, Hope Center for Neurological Disorders, Washington University School of Medicine, St. Louis, MO 63110, USA

Received 13 April 2014; Revised 30 June 2014; Accepted 1 July 2014; Published 14 August 2014

Academic Editor: Stephen D. Ginsberg

Copyright © 2014 Anne M. Fagan. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.


Data from clinicopathologic and biomarker studies have converged to support the view of Alzheimer’s disease (AD) as a continuum, with pathology developing decades prior to the onset of cognitive symptoms which culminate as dementia at the end stage of the disease. This concept is impacting disease nomenclature, diagnostic criteria, prognostic potential, and clinical trial design. Revisions to diagnostic criteria to incorporate biomarker results have recently been proposed in order to increase the confidence of AD as the underlying etiology of a clinical impairment and to permit a diagnosis of AD across the disease continuum, eventually perhaps in the asymptomatic period. Individuals in this preclinical stage are receiving intense focus as a targeted population for secondary prevention trials aimed at identifying disease-modifying therapies that have the best chance of preserving normal cognitive function. The goal is to bring validated biomarkers to clinical practice for the purpose of disease diagnosis, prognosis, and evaluation of therapeutic efficacy once disease-modifying treatments become available. Realization of this goal requires worldwide biomarker standardization efforts, consensus among researchers and clinicians regarding the clinical utility of assessing biomarkers in patient care settings, and eventually the endorsement and adoption of such procedures and practices into global health care systems.