Abstract

Advances in our understanding of the mechanisms of tau-mediated neurodegeneration in Alzheimer's disease (AD) and related tauopathies, which are characterized by prominent CNS accumulations of fibrillar tau inclusions, are rapidly moving this previously underexplored disease pathway to centre stage for disease-modifying drug discovery efforts. However, controversies abound concerning whether or not the deleterious effects of tau pathologies result from toxic gains-of-function by pathological tau or from critical losses of normal tau function in the disease state. This Review summarizes the most recent advances in our knowledge of the mechanisms of tau-mediated neurodegeneration to forge an integrated concept of those tau-linked disease processes that drive the onset and progression of AD and related tauopathies.

Author affiliations

1. Center for Neurodegenerative Disease Research, Department of Pathology and Laboratory Medicine, University of Pennsylvania, 3600 Spruce Street, Philadelphia, Pennsylvania 19104-4283, USA.
2. Institute on Aging, University of Pennsylvania, 3615 Chestnut Street, Philadelphia, Pennsylvania 19104-2676, USA.
3. Department of Chemistry, University of Pennsylvania, 231 South 34th Street, Philadelphia, Pennsylvania 19104-6323, USA.

Correspondence to: John Q. Trojanowski^1,2 Email: trojanow@mail.med.upenn.edu

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