D-TLKIVWC

PS19 transgenic mice (P301S mutant human tau; Prnp-MAPT*P301S PS19Vle/J, JAX #008169; 2-month-old male and 6-month-old female cohorts)^[2]

10 mg/kg

i.v. via tail vein; once weekly; for 10 weeks; starting 2 weeks after stereotaxic seeding; combined with intranasal mannitol

In tau-seeded PS19 mice (n = 13 per group; 8 male and 5 female mice per group), body-weight loss associated with late-stage tau pathology was prevented over the 10-week dosing period.
In the Barnes maze, PS19 mice showed shorter learning latency to find the escape hole than vehicle or naked MNP control PS19 mice.
In the probe trial, latency, target-hole entries, and search paths were comparable to wild-type mice and improved relative to PBS control PS19 mice.
In the novel object recognition test, PS19 mice explored the novel object longer than the familiar object and showed improved discriminatory index and discriminatory ratio versus vehicle control PS19 mice.
AT8 immunohistochemistry showed reduced phosphorylated tau pathology in CA1 and CA3 regions relative to vehicle or naked MNP control mice.
Western blot analysis showed decreased RIPA-soluble and RIPA-insoluble phosphorylated tau levels in PS19 mouse brain (n = 8 per group).