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Co-expression of truncated and full-length tau induces severe neurotoxicity

Abramowski, Dorothee and Staufenbiel, Matthias (2016) Co-expression of truncated and full-length tau induces severe neurotoxicity. Mol Psychiatry. ISSN 1359-4184


Abundant tau inclusions are a defining hallmark of several human neurodegenerative
diseases, including Alzheimer’s disease. Although studied widely, the relevance of tau
fragmentation for the neurodegenerative process has remained unclear. Here we found that
co-expression of truncated and full-length human tau in mice provoked the formation of
soluble high-molecular weight tau, the failure of axonal transport, clumping of mitochondria,
disruption of the Golgi apparatus, and missorting of synaptic proteins. This was associated
with extensive nerve cell dysfunction and severe paralysis by the age of 3 weeks. When the
expression of truncated tau was halted, most mice recovered behaviorally and functionally. In
contrast, co-expression of full-length tau isoforms did not result in paralysis. Truncated tau
thus induces extensive but reversible neurotoxicity in presence of full-length tau through the
formation of non-filamentous high-molecular weight tau aggregates. Targeting tau
fragmentation may provide a novel approach for the treatment of human tauopathies.

Item Type: Article
Date Deposited: 27 Apr 2016 23:45
Last Modified: 27 Apr 2016 23:45


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