Prion-like Spreading in Tauopathies

Biological Psychiatry
Jacob I AyersDavid R Borchelt

Abstract

Tau is a microtubule-associated protein that functions in regulating cytoskeleton dynamics, especially in neurons. Misfolded and aggregated forms of tau produce pathological structures in a number of neurodegenerative diseases, including Alzheimer's disease (AD) and tauopathy dementias. These disorders can present with a sporadic etiology, such as in AD, or a familial etiology, such as in some cases of frontotemporal dementia with parkinsonism. Notably, the pathological features of tau pathology in these diseases can be very distinct. For example, the tau pathology in corticobasal degeneration is distinct from that of an AD patient. A wealth of evidence has emerged within the last decade to suggest that the misfolded tau in tauopathies possesses prion-like features and that such features may explain the diverse characteristics of tauopathies. The prion-like concept for tauopathies arose initially from the observation that the progressive accumulation of tau pathology as the symptoms of AD progress seemed to follow anatomically linked pathways. Subsequent studies in cell and animal models revealed that misfolded tau can propagate from cell to cell and from region to region in the brain through direct neuroanatomical connections....Continue Reading

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