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Fig. 11 | Acta Neuropathologica Communications

Fig. 11

From: Tau isoforms are differentially expressed across the hippocampus in chronic traumatic encephalopathy and Alzheimer’s disease

Fig. 11

Working hypothesis model of 4R to 3R shift that occurs in mixed 3R/4R tauopathies. The current working hypothesis behind the evolution of the tau phenotype across disease severity is likely due to 3R strongly capturing ghost tangle pathology. Pretangles are believed to begin as a predominant 4R phenotype. Over the course of an NFT lifecycle, although the fibril structure is long lived, tau has been observed to be dynamic with monomers and oligomers constantly being added and replaced. Through a still unclear mechanism, there is a switch which results in more 3R tau being incorporated to the NFT as pathology becomes more severe. At the end stage, the ghost tangle is primarily composed of 3R tau. These findings have been seen across CTE and AD suggesting this phenotype is not specific to a unique pathology, rather, it is identifying something about the fundamental biology of mixed 3R/4R pathologies as a whole

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