. CSF p-tau increase in response to Aβ-type and Danish-type cerebral amyloidosis and in the absence of neurofibrillary tangles. Acta Neuropathol. 2022 Feb;143(2):287-290. Epub 2021 Dec 28 PubMed.

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  1. This interesting report suggests that CSF t-tau, P-tau181 and -217 are elevated in response to a variety of amyloid species, and that this elevation may occur similarly in mouse models and humans, even if the mice do not develop insoluble tau pathology. The data are supportive of a model whereby amyloid leads to elevated production of soluble tau species, which might potentially be a prerequisite for deposition of insoluble tau species in humans.

    It is encouraging that the relationship between amyloid and soluble tau species can be recapitulated in transgenic mice, thereby providing a model system for understanding the mechanisms by which elevated amyloid leads to elevated tau. 

    However, the relationship between soluble tau species and insoluble tau deposition (NFT and other aggregates) still remains unclear. While there are strong correlations between the two in humans, much work will be needed to understand how these different tau species relate to each other and to the clinical symptoms of tauopathies.  Understanding this relationship will be key for developing more efficient clinical trials and monitoring the response to novel AD therapeutics.

    View all comments by Adam Boxer

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