Fig. 2.

Exacerbation of learning and memory deficit in APP⁺-ob/ob mice, without increase in brain Aβ load. (A–D) Morris water maze test at 8 weeks. Escape latencies in hidden-platform (A) and visible-platform (B) test, number of annulus crossings (C), and representative swim paths (D) during the probe test are shown (n = 11–17 per group). **P < 0.01 for APP⁺-ob/ob mice versus other genotypes. “Target” indicates the area where the platform was constantly located in the hidden-platform test. (E and F) Morris water maze test at 12 weeks. Escape latencies in hidden-platform (E) and visible-platform (F) test (n = 11–13). *P < 0.05, **P < 0.01. (G and H) Quantification of brain Aβ40 and Aβ42 concentrations. Both Triton-X–soluble (G) and -insoluble (guanidine extract) (H) Aβ were measured (n = 6–7). (I) Aβ immunostaining (6E10) in brain of APP⁺ and APP⁺-ob/ob mice. There was no detectable amyloid plaque at this early age (12 weeks) in either genotype. (Scale bar, 200 μm.)