Identifying and validating biomarkers for Alzheimer's disease

Abstract

The identification and validation of biomarkers for diagnosing Alzheimer's disease (AD) and other forms of dementia are increasingly important. To date, ELISA measurement of β-amyloid(1-42), total tau and phospho-tau-181 in cerebrospinal fluid (CSF) is the most advanced and accepted method to diagnose probable AD with high specificity and sensitivity. However, it is a great challenge to search for novel biomarkers in CSF and blood by using modern potent methods, such as microarrays and mass spectrometry, and to optimize the handling of samples (e.g. collection, transport, processing, and storage), as well as the interpretation using bioinformatics. It seems likely that only a combined analysis of several biomarkers will define a patient-specific signature to diagnose AD in the future.

Figure 1

The principal steps necessary for AD biomarker discovery (left flowchart) and for routine analysis of CSF samples (right flowchart). Similar steps are shown in red boxes. Only a good clinical diagnosis is the basis for statistical analysis of biomarker discovery. To date, laboratory diagnosis only supports the clinical diagnosis, which cannot be regarded as a stand-alone diagnostic tool.