Fig. 4. Assessment of cognitive decline in APP/PS1 Tg mice through Morris water maze and nesting building tests.

Five-month-old APP/PS1 Tg mice were treated with small EVs or macrosomes (200 μg kg⁻¹) for 4 weeks through nasal feeding daily. (A) Latency for escape to visible platform and hidden platform. (B) Numbers of the target crossings in the test. (C) Representative images of track of probe test. (D and E) Representative images of nesting building and scores observed for seven consecutive days. n = 6 mice: WT group; n = 10 mice: APP/PS1, small EV, and macrosome groups. Error bars, means ± SD, one-way ANOVA, Tukey’s test. *P < 0.05, **P < 0.01, and ***P < 0.001.