The human islet amyloid polypeptide reduces hippocampal tauopathy and behavioral impairments in P301S mice without inducing neurotoxicity or seeding amyloid aggregation

Recent evidence suggests that human islet amyloid polypeptide (h-IAPP) accumulates in the brains of Alzheimer's disease (AD) patients and may interact with A beta or microtubule associated protein tau to associate with the neurodegenerative process. Increasing evidence indicates a potential protective effect of h-IAPP against A beta-induced neurotoxicity in AD mouse models. However, a direct therapeutic effect of h-IAPP supplementation on tauopathy has not been established. Here, we found that long-term h-IAPP treatment attenuated tau hyperphosphorylation levels and induced neuroinflammation and oxidative damage, prevented synaptic loss and neuronal degeneration in the hippocampus, and alleviated behavioral deficits in P301S transgenic mice (a mouse model of tauopathy). Restoration of insulin sensitization, glucose/energy metabolism, and activated BDNF signaling also contributed to the underlying mechanisms. These findings suggest that seemly h-IAPP has promise for the treatment of neurodegenerative disorders with tauopathy, such as AD.

Automated summary

Recent evidence suggests that human islet amyloid polypeptide (h-IAPP) may interact with A β or tau in Alzheimer's disease (AD) and have a potential therapeutic effect on neurodegenerative disorders with tauopathy, such as AD. Long-term h-IAPP treatment attenuated tau hyperphosphorylation levels, induced neuroinflammation and oxidative damage, prevented synaptic loss and neuronal degeneration, and alleviated behavioral deficits in a mouse model of tauopathy.