[Biomarkers for the differential diagnosis of corticobasal syndrome]

Corticobasal degeneration (CBD) is a progressive neurodegenerative disorder characterized by progressive, asymmetric, cortical (e.g., apraxia, alien limb phenomena, myoclonus, etc.) and extrapyramidal (e.g., rigidity, bradykinesia, dystonia, etc) symptoms. CBD was initially thought to represent a clinicopathological entity, but recent studies have shown its considerable clinicopathological heterogeneity. Thus, the constellation of the findings initially considered characteristic of CBD is now named "corticobasal syndrome" (CBS), while the term "CBD" is used for the histopathological disorder. Multiple phenotypes associated with CBD pathology and multiple diseases associated with CBS, the latter of which are called "CBD mimickers", make the correct diagnosis of these conditions on the basis of only clinical symptoms and signs difficult. Therefore, the development of specific biomarkers for diagnosing each causative disease of CBS is extremely important. Abnormal accumulations of the microtubule-associated tau protein are found in both neurons and glia, and CBD is thus considered one of the tauopathies. Although some studies have measured total and phosphorylated tau in the cerebrospinal fluid (CSF) of patients with CBS, their results are inconclusive. The aim of this article is to provide some clues for differential diagnosis of diseases causing CBS and to review studies on biochemical and genetic biomarkers for those disorders. Disease-specific truncation and/or phosphorylation of tau protein and its fragments in the CSF would be a promising biomarker candidate; however, its effectiveness still needs to be confirmed by further studies. Progress in biomarker development to differentiate CBD from CBD mimickers has been slow, but it is essential to improve diagnostic accuracy and to develop disease-modifying therapies.