Fig. 5

hAPP₆₉₅ (hAPP), but not hAPP-swe, effectively rescued defects in axonal outgrowth in APPb-MO morphants.

(A) Co-injection of hAPP₆₉₅ mRNA rescued APPb morphant embryonic morphology. As depicted, embryos were inspected over a period of 3 days. Co-injection of full length human APP₆₉₅ mRNA rescued the defective phenotype observed in the APPb morphant embryos (*, p = 0.026, p<0.05 in two tailed paired t-test). In contrast, human APP-Swedish mutation (Δ, p = 0.5241, p>0.05) and AICD mRNA failed to rescue the APPb morphant phenotype. Combined injections (10 ng of APPb-MO and 350 pg of AICD mRNA) caused more severe deficits compared to injecting APPb-MO alone. (B) Co-injection of hAPP₆₉₅ mRNA rescued axonal outgrowth of motor neurons Vp and VII of the APPb morphant. Zebrafish embryos co-injected with full length human APP₆₉₅ rescued the APPb morphant axonal outgrowth phenotype of motor neurons Vp and VII (arrow). (C) Embryos co-injected with hAPP₆₉₅ rescued the defective phenotype of motor axons in the spinal cord in APPb morphant embryos. Uninjected embryos expressed normal motor neuron projections from the spinal cord to the myotomes (5–10 somites). Embryos injected with (10 ng) APPb-MO expressed severe motor neuron axonal defects including aberrant projections and decreased branching. Embryos co-injected with APPb-MO and hAPP₆₉₅ mRNA had a rescued phenotype compared to the morphant group. Lateral views of 3 dpf embryos (anterior is to the left, dorsal is at the top). (D) Quantification of embryos expressing normal axonal outgrowth of neurons Vp and VII and spinal cord rescued through co-injection of hAPP695 mRNA. Injection of 10 ng of APPb-MO caused abnormal axonal outgrowth of motor neurons Vp and VII in 75% of embryos. Co-injection with mRNA encoding full-length human APP695 overwhelmingly rescued the APPb morphant phenotype (p = 0.0075, p<0.05 in two tailed paired t-test) (3 dpf). Embryos injected with 10 ng APPb-MO showed significant inhibition of spinal cord axon outgrowth. Embryos co-injected with 10 ng of APPb-MO and 350 pg of hAPP695 mRNA rescued the APPb morphant phenotype (p = 0.0101, p<0.05 in two tailed paired t-test).