Why do AD and CTE tau prions fail to robustly infect single isoform-expressing cells despite containing both 3R and 4R tau?

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Description

The abstract shows that AD/CTE prions containing both tau isoforms cannot efficiently infect cells expressing only 3R or 4R tau, contradicting expectations that mixed prions should interact with either isoform. This suggests unknown conformational or structural constraints that could inform therapeutic targeting.

Gap type: contradiction Source paper: Tau prions from Alzheimer’s disease and chronic traumatic encephalopathy patients propagate in cultured cells. (2016, Proceedings of the National Academy of Sciences of the United States of America, PMID:27911827)

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