Human placenta extract ameliorates memory dysfunction and dendritic atrophy in a 5XFAD mouse model of Alzheimer's disease

Aim: In this study, we investigated the effects of a human placenta-derived drug, Laennec (Japan Bio Products), on memory improvement and neuritic regeneration in Alzheimer's disease model mice, to evaluate the potential of Laennec as a new candidate for anti-Alzheimer's disease (AD) therapy. Methods: The anti-AD effects of Laennec were evaluated using amyloid β (Aβ)-treated cortical neurons and the 5XFAD mouse model of AD. Results: Laennec significantly improved the dendritic density in normal cortical neurons but not the axon density. Exposure to the peptide fragment Aβ(25–35) for 3 days resulted in significant atrophy in the axons and dendrites of cortical neurons (ddY mice, E14). Laennec significantly improved the density and dendritic length of the Aβ-treated cortical neurons but did not affect axon atrophy. Synaptic loss induced by Aβ(25–35) was also completely reversed by Laennec treatment. The Laennec-treated 5XFAD mice (for 15 days, i.p. or p.o.; 5–7 months old, female) showed significant improvement in object recognition memory, but had no reduction in amyloid plaques in the perirhinal cortex, although the reduced dendritic density in the amyloid plaque-associated sites was significantly increased by Laennec treatment. Furthermore, the components of Laennec were separated based on their molecular weights using ultrafiltration. The Laennec fraction >2 kDa contained the active compounds for dendrite extension. Conclusion: Laennec improved object recognition memory and dendritic growth in a model of AD.