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. 2021 Mar 19;7(12):eabe1611. doi: 10.1126/sciadv.abe1611

Fig. 5. Rapid brain tau reduction after a single systemic injection of AAV-PHP.B ZFP-TFs.

Fig. 5

(A) Brain sections from mice with a single intravenous (IV) injection of PHP.B hSyn1.GFP show transduction of neurons in various brain regions and spinal cord. Injection of the same dose of AAV-PHP.B CMV.89v also achieves brain-wide expression. (B) Experimental overview of time course of tau reduction using AAV-PHP.B hSyn1.89v and hSyn1.90v. (C) Tau mRNA levels in cortex, hippocampus, and cerebellum of PHP.B hSyn1.89v– and 90v-injected animals from 0 to 24 weeks. PHP.B hSyn1.GFP and PHP.B hSyn1.72v did not reduce tau mRNA. Means ± SEM, two-way ANOVA versus PBS, n = 3 to 8 mice per group and time point, three tissue samples per region and measurement. P value indication: * for 89v; # for 90v. Note that the unexpected low tau mRNA levels in the cerebellum after 4 weeks do not reflect in tau protein levels. (D) Tau protein levels (by ELISA) in cortex, hippocampus, cerebellum, and CSF of PHP.B hSyn1.89v– and 90v-injected animals from 0 to 24 weeks. PHP.B hSyn1.GFP and PHP.B hSyn1.72v did not reduce tau protein. Means ± SEM, two-way ANOVA versus PBS, n = 3 to 8 mice per group and time point, three tissue samples per region and measurement. P value indication: * for 89v; # for 90v.