Du M, Akerman SC, Fare C, Ruan L, Vidensky S, Mamedova L, Lee J, Rothstein JD. Divergent and Convergent TMEM106B Pathology in Murine Models of Neurodegeneration and Human Disease. 2024 Oct 18 10.1101/2024.10.16.618765 (version 1) bioRxiv.
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University of Kiel
Interesting story, if true: So far, TMEM106B fibrils have not been demonstrated in mice. Some critical controls are missing in this preprint: the current set of antibodies cannot distinguish between fibrillary/physiological (natively folded) TMEM106B. The punctate staining pattern suggests these are not fibrils but rather the properly folded TMEM106B in lysosomes. The staining pattern in human patient material looks strikingly different with mostly astrocytic TMEM106B-inclusions. The polyclonal antiserum/antibodies could also be unspecific on mouse brain tissue.
Given the relevance and novelty of TMEM106B fibrils in mice, additional evidence should be included, e.g., by Sarkosyl extraction of fibrillary material and immunoblotting.
The study also underscores the need for fibril-specific TMEM106B antibodies.
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