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P3‐051: Novel Alzheimer’s Therapeutics Candidate SAK3 Enhances the ACH Release and LTP Induction in the Hippocampus
Author(s) -
Fukunaga Kohji,
Yabuki Yasushi
Publication year - 2016
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.2016.06.1709
Subject(s) - hippocampus , hippocampal formation , long term potentiation , neuroscience , voltage dependent calcium channel , chemistry , pharmacology , medicine , psychology , calcium , receptor
abnormalities (ARIA) is problematic in many of these trails. This toxicity is in part related to the effector function of the antibodies used. Recently, an affibody molecule that lacks effector function, but binds to monomeric Ab peptides, with aggregation inhibition capacity, was generated and tested in AD model transgenic fruit flies, demonstrating abolition of Ab related neurotoxic effects and restoration of their life span. Here we assessed the efficacy of passive immunization with the affibody in a mouse model of AD. Methods: APP/ PS1 transgenic AD model mice were injected intraperitoneally twice a week with the Ab-binding ZSYM73-ABD Affibody molecule from the age of 6 months (at a point where the mice already have amyloid deposition). Control mice received a non-Ab binding affibody. Their behavior was assessed at 9 months of age and brain tissue subsequently was harvested for analysis of treatment efficacy. Results: The treated (Ab-binding ZSYM73-ABD) mice didn’t show a significant difference from controls on locomotor testing. ZSYM73ABD treated-mice performed the same as wild-type mice. The amyloid burden of in treated animals was reduced by 49 % in the cortex and 50% in the hippocampus. There was no significant difference in astrogliosis or microhemorrhages between treated and control mice. Conclusions:These results indicate that passive immunization with an Affibody molecule can significantly decrease the amyloid burden and improve cognitive function in a transgenic mouse model of AD.