The Role of Cerebrospinal Fluid Biomarkers in the Evolution of Diagnostic Criteria in Alzheimer's Disease: Shortcomings in Prodromal Diagnosis

The available evidence indicates a high performance of core cerebrospinal fluid (CSF) biomarkers in differentiating between Alzheimer's disease (AD) and other dementias, and suggests that their characteristic alterations can be detected even at the prodromal stage of AD. On this basis, the ability of core CSF biomarkers to identify prodromal AD patients from pre-dementia of all causes can be postulated, a concept that is reflected in recent revisions of AD research criteria and a consensus statement. Following an overview on the role of biomarkers in the evolution of diagnostic criteria of AD in recent decades, this paper provides a critical review of the widely applied CSF biomarker study designs and evaluating approaches that address the ability of core CSF biomarkers to diagnose prodromal AD, with special focus on their potential limitations in terms of clinical interpretation and utility. The findings together raise the question of whether we are indeed able to establish a CSF biomarker-based diagnosis of AD at the prodromal stage.