Emerging Diagnostic and Therapeutic Strategies for Tauopathies

David Coughlin, David J. Irwin

Tauopathies represent a spectrum of incurable and progressive age-associated neurodegenerative diseases that currently are diagnosed definitively only at autopsy. Few clinical diagnoses, such as classic Richardson's syndrome of progressive supranuclear palsy, are specific for underlying tauopathy and no clinical syndrome is fully sensitive to reliably identify all forms of clinically manifest tauopathy. Thus, a major unmet need for the development and implementation of tau-targeted therapies is precise antemortem diagnosis. This article reviews new and emerging diagnostic therapies for tauopathies including novel imaging techniques and biomarkers and also reviews recent tau therapeutics. Building evidence from animal and cell models suggests that prion-like misfolding and propagation of pathogenic tau proteins between brain cells are central to the neurodegenerative process. These rapidly growing developments build rationale and motivation for the development of therapeutics targeting this mechanism through altering phosphorylation and other post-translational modifications of the tau protein, blocking aggregation and spread using small molecular compounds or immunotherapy and reducing or silencing expression of the MAPT tau gene. New clinical criteria, CSF, MRI, and PET biomarkers will aid in identifying tauopathies earlier and more accurately which will aid in selection for new clinical trials which focus on a variety of agents including immunotherapy and gene silencing.