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P3‐058: CONSTITUTIVELY ACTIVE DUAL LEUCINE ZIPPER KINASE (DLK) REGULATES SYNAPTIC MAINTENANCE IN UNINJURED MOUSE CEREBELLUM
Author(s) -
Goodwani Sunil,
Acton Paul,
Buggia-Prevot Virginie,
Chakraborty Chaitali,
Fernandez Celia,
Hamby Mary,
Lightfoot Yaima Luzardo,
McReynolds Morgan,
Al-Ouran Rami,
Soth Michael,
Jones Philip,
Ray Jim
Publication year - 2018
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.2018.06.1414
Subject(s) - cerebellum , forebrain , biology , microbiology and biotechnology , neuroscience , axon , neurodegeneration , signal transduction , central nervous system , medicine , disease
C57BL/6 wild-type mice treated with saline (n1⁄48) with identical regiment. At 9 weeks following treatment initiation, exploration and spatial memory were assessed with the open-field and Ymaze test, mice were sacrificed, and brains were evaluated for Ab peptide load, synaptic loss, microglial activation and microhemorrhages. Results: Mice treated with the BBB-penetrable cTfRMAb-EPO fusion protein had significantly lower cortical and hippocampal Ab peptide number (p<0.05) and immune-positive area (p<0.05), a decrease in hippocampal synaptic loss (p<0.01) and cortical microglial activation (p<0.001), and improved spatial memory (p<0.01) compared with APP/PS1 saline controls. BBB-penetrating EPO was not associated with microhemorrhage development. Conclusions: Treatment with the BBBpenetrating cTfRMAb-EPO fusion protein offered therapeutic benefits by targeting multiple targets of AD pathogenesis and progression (Ab load, synaptic loss, microglial activation) and improving spatial memory recognition in the APP/PS1 mouse model of AD.