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Annu Rev Neurosci. 2017 Jul 25;40:189-210. doi: 10.1146/annurev-neuro-072116-031153.

Propagation of Tau Aggregates and Neurodegeneration.

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MRC Laboratory of Molecular Biology, Cambridge CB2 0QH, United Kingdom; email:
Department of Biological Chemistry and Howard Hughes Medical Institute, University of California, Los Angeles, California 90095.


A pathway from the natively unfolded microtubule-associated protein Tau to a highly structured amyloid fibril underlies human Tauopathies. This ordered assembly causes disease and represents the gain of toxic function. In recent years, evidence has accumulated to suggest that Tau inclusions form first in a small number of brain cells, from where they propagate to other regions, resulting in neurodegeneration and disease. Propagation of pathology is often called prion-like, which refers to the capacity of an assembled protein to induce the same abnormal conformation in a protein of the same kind, initiating a self-amplifying cascade. In addition, prion-like encompasses the release of protein aggregates from brain cells and their uptake by neighboring cells. In mice, the intracerebral injection of Tau inclusions induces the ordered assembly of monomeric Tau, followed by its spreading to distant brain regions. Conformational differences between Tau aggregates from transgenic mouse brain and in vitro assembled recombinant protein account for the greater seeding potency of brain aggregates. Short fibrils constitute the major species of seed-competent Tau in the brains of transgenic mice. The existence of multiple human Tauopathies with distinct fibril morphologies has led to the suggestion that different molecular conformers (or strains) of aggregated Tau exist.


Alzheimer's disease; Pick's disease; Tau; Tauopathies; amyloid; cell-to-cell spreading; disease propagation; prion-like; protein strains; toxicity

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