Why does the protective TMEM106B T185S variant fail to show protection in mouse models despite human genetic evidence?

neurodegeneration open
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Description

Human genetic studies consistently show the T185S variant is protective in FTLD-GRN carriers, yet this study found no protective effect in Grn knockout mice. This species-specific discordance suggests critical differences in disease mechanisms or variant function that could impact translational research.

Gap type: contradiction Source paper: Lack of a protective effect of the Tmem106b “protective SNP” in the Grn knockout mouse model for frontotemporal lobar degeneration. (2023, Acta neuropathologica communications, PMID:36707901)

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