Abstract
The accumulation of tau protein in the form of filamentous aggregates is a hallmark of many neurodegenerative diseases such as Alzheimer’s disease (AD) and chronic traumatic encephalopathy (CTE). These dementias share traumatic brain injury (TBI) as a prominent risk factor. Tau aggregates can transfer between cells and tissues in a “prion-like” manner, where they initiate the templated misfolding of normal tau molecules. This enables the spread of tau pathology to distinct parts of the brain. The evidence that tauopathies spread via prion-like mechanisms is considerable, but work detailing the mechanisms of spread has mostly used in vitro platforms that cannot fully reveal the tissue-level vectors or etiology of progression. We review these issues and then briefly use TBI and CTE as a case study to illustrate aspects of tauopathy that warrant further attention in vivo. These include seizures and sleep/wake disturbances, emphasizing the urgent need for improved animal models. Dissecting these mechanisms of tauopathy progression continues to provide fresh inspiration for the design of diagnostic and therapeutic approaches.
Highlights
Pathological tau aggregation is the defining characteristic for a subset of devastating neurodegenerative disorders collectively called tauopathies
We reviewed the biochemical aspect of tau aggregation and the prion-like spreading of tauopathies as a key element in the progression of devastating dementias
The observations and data collected from diverse sources, including patients, cells, and animal models, have all led to the generation and support of the prion-like hypothesis of tauopathy progression
Summary
Pathological tau aggregation is the defining characteristic for a subset of devastating neurodegenerative disorders collectively called tauopathies. The microtubule-associated protein tau undergoes a plethora of changes at both the molecular and structural level, leading to the production of abnormal aggregates. These aggregates can take on the form of oligomers or larger filaments that assemble into neurofibrillary or glial fibrillary tangles [1,2,3]. Recent studies demonstrate support for the prion-like hypothesis that tau protein pathology can be spread between tissues or brain regions [7]. We evaluate recent evidence supporting the prion-like spreading of tau pathology, noting knowledge gaps and opportunities regarding traumatic brain injury (TBI) and chronic traumatic encephalopathy (CTE) (Section 3).
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