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P4‐205: Peripheral administration of the novel tnf inhibitor xpro1595 improves synaptic function in the 5XFAD model of Alzheimer's disease
Author(s) -
Norris Christopher M.,
Sompol Pradoldej,
MacPherson Kathryn P.,
Tansey Malu G.
Publication year - 2015
Publication title -
alzheimer's and dementia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 6.713
H-Index - 118
eISSN - 1552-5279
pISSN - 1552-5260
DOI - 10.1016/j.jalz.2015.08.033
Subject(s) - synaptic plasticity , long term potentiation , neuroprotection , tumor necrosis factor alpha , excitatory postsynaptic potential , stimulation , neuroscience , receptor , nmda receptor , endocrinology , medicine , pharmacology , chemistry , biology
using immunoblotting and immunohistochemistry. 5XFAD transgenic mice were crossed with AEP knockout mice to determine the effect of AEP on the aggregation of Ab. Results:AEP cleaves APP at N373 and N585 residues, selectively influencing the amyloidogenic fragmentation of APP. AEP is activated in normal mice in an age-dependent manner, and is strongly activated in 5XFAD transgenic mouse model and human AD brains. AEP interacts with APP in the endolysosomal organelles. Deletion of AEP from 5XFADmice decreases senile plaque formation, ameliorates synapse loss and elevates long-term potentiation, leading to protection of memory loss. Conclusions:AEP mediates the proteolytic processing of APP, contributing to the amyloidogenesis in AD.