Abstract：
:Prion-like propagation of tau aggregation might underlie the stereotyped progression of neurodegenerative tauopathies. True prions stably maintain unique conformations ("strains") in vivo that link structure to patterns of pathology. We now find that tau meets this criterion. Stably expressed tau repeat domain indefinitely propagates distinct amyloid conformations in a clonal fashion in culture. Reintroduction of tau from these lines into naive cells reestablishes identical clones. We produced two strains in vitro that induce distinct pathologies in vivo as determined by successive inoculations into three generations of transgenic mice. Immunopurified tau from these mice recreates the original strains in culture. We used the cell system to isolate tau strains from 29 patients with 5 different tauopathies, finding that different diseases are associated with different sets of strains. Tau thus demonstrates essential characteristics of a prion. This might explain the phenotypic diversity of tauopathies and could enable more effective diagnosis and therapy.
journal_name
Neuronjournal_title
Neuronauthors
Sanders DW,Kaufman SK,DeVos SL,Sharma AM,Mirbaha H,Li A,Barker SJ,Foley AC,Thorpe JR,Serpell LC,Miller TM,Grinberg LT,Seeley WW,Diamond MIdoi
10.1016/j.neuron.2014.04.047subject
Has Abstractpub_date
2014-06-18 00:00:00pages
1271-88issue
6eissn
0896-6273issn
1097-4199pii
S0896-6273(14)00362-6journal_volume
82pub_type
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