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SORLA upregulation suppresses global pathological effects in aged tauopathy mouse brain [snRNA-seq]

GSE278215 Mus musculus Expression profiling by high throughput sequencing 4 samples Submitted 2026/05/24 Platform GPL24247
Summary
A role for the type I transmembrane trafficking receptor SORLA in reducing Aβ levels has been well-established, however, virtually nothing is known with respect to whether and how SORLA can potentially affect tau pathology. Here, we show that transgenic SORLA upregulation (SORLA TG) can reverse pathological effects in aged PS19 (P301S tau) mouse brain, including tau phosphorylation, ventricle dilation, synapse loss, LTP impairment and glial hyperactivation. Proteomic analysis indicates reversion of PS19 profiles in PS19/SORLA TG hippocampus, including pathological changes in synapse-related proteins as well as key drivers of synaptic dysfunction such as Apoe and C1q. snRNAseq analysis reveals suppression of PS19-dependent signatures with SORLA upregulation, including proinflammatory induction of Plxnb1/Plxnb2 in glial cell types. PlxnB1/B2 expression as well as other neuroinflammatory features are exacerbated in PS19 hippocampus with SORLA deletion. Together, these results implicate a global role for SORLA in neuroprotection from tau toxicity in PS19 mouse brain.
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Also filed as BioProject PRJNA1166116 and SRA study SRP535261. Searching any of these in the dataset finder brings you back here.

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