Fig. 7. TAT1-8,9TOD reduces cognitive deficits, proteostatic dysfunction, and abundance of Aβ machinery in hAPP(J20) mice.

(A) Treatment of MC65 cells with TAT1-8,9TOD reduces AD-related cell death, based on WST-1 viability assay, N = 24. (B) Proteasome activity in the brain of nontransgenic mice 24 hours after intraperitoneal injection with TAT1-8,9TOD, N = 5. (C) Treatment schematic; 6-month-old hAPP(J20) mice were treated every 2 days for 14 days with intraperitoneal injections of TAT1-8,9TOD (1.26 mg/kg) or vehicle (N = 5). (D) Novel object recognition assay in TAT1-8,9TOD–treated hAPP(J20) mice. (E) Representative immunoblot. (F and G) Immunoblots and ELISA of brain tissue from TAT1-8,9TOD–treated hAPP(J20) against (F) anti-APP, (G) anti-BACE1, (H) Aβ₄₂ ELISA, (I) anti–K48-polyubiquitinated proteins, and (J) anti–K63-polyubiquitinated proteins. Values normalized by β-actin. *P < 0.05 and **P < 0.01. Significance was based on one- or two-way ANOVA in (A) and (B). Student’s t test was used in (D) to (J). N represents the number of animals or samples per group.