Assessment of pathological tau proteins in frontotemporal dementias: qualitative and quantitative approaches

A large group of clinically and neuropathologically heterogeneous frontotemporal dementias (FTDs) is distinguished by the accumulation of filamentous tau proteins in neuronal and non-neuronal cells, and these disorders are collectively designated as tauopathies. Recent advances in the development of new reagents and the utilization of new multidisciplinary approaches have made substantial progress in the extensive characterization of tau proteins in different tauopathies. Until recently, semi-quantitative assessment of specific pathological lesions in FTDs was limited to immunohistochemical methods. However, it has become increasingly evident that biochemical analyses of pathological tau proteins in diseased brains also play a significant role in establishing the diagnosis of specific FTD subtypes. In this review, the authors summarize recent findings of the unique biochemical tau signatures for a number of specific tauopathies. Moreover, the quantitative assessment of abnormal tau proteins described here reveals heterogeneity in the biochemical features of tau pathologies in FTDs. The identification of highly insoluble tau species that may be more prone to physiological clearance, other than those that form paired helical filaments, could provide additional insights into the role of tau in mechanisms of neurodegeneration in FTDs.