Cerebrospinal fluid brain‐derived proteins in the diagnosis of Alzheimer's disease and Creutzfeldt–Jakob disease

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Abstract
The differential diagnosis of dementia can be difficult in the early stages of disease, and with the emergence of new therapeutic agents for Alzheimer's disease (AD) there is an increasing need for reliable and accurate diagnostic tests. The concept of brain‐specific proteins was first proposed in the 1960s and, since that time, methods have developed to measure these proteins in the cerebrospinal fluid (CSF). The concentration of individual brain‐specific proteins can be altered in disease, and these changes are thought to reflect the underlying pathology. CSF tau protein and amyloid peptide Aβ42 concentrations are altered in AD and have been proposed as early diagnostic tests for this disease. The data from a number of studies suggest that these proteins may be of value, but are less specific than previously thought and further studies with neuropathological confirmation are required before these tests can be introduced into clinical practice. The detection of 14‐3‐3 in the CSF is an accurate test for sporadic Creutzfeldt–Jakob disease (CJD) and this accuracy has lead the World Health Organization to revise the clinical criteria for probable sporadic CJD to include a positive CSF 14‐3‐3. However, CSF 14‐3‐3 is less useful in the diagnosis of variant CJD, where studies are underway investigating the value of other CSF proteins.