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Regulation of amyloid‐beta pathology by CNS amylin receptors in APP/PS1 mice
Author(s) -
Corrigan Rachel,
Grizzanti John,
Casadesus Gemma
Publication year - 2020
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 - 10.1002/alz.044229
Subject(s) - amylin , hippocampal formation , medicine , endocrinology , amyloid precursor protein , hippocampus , amyloid (mycology) , receptor , blockade , neuroscience , insulin , biology , alzheimer's disease , pathology , disease , islet
Abstract Background Amylin is a pancreatic amyloid protein, known to regulate glucose homeostasis and satiety through its ability to sensitize insulin and leptin. Importantly, the amylin receptor (AMYR) is expressed throughout the brain, including areas important in both cognition and Alzheimer’s disease (AD) pathology, like the hippocampus. We and others have previously shown that an analogue of amylin, Pramlintide (PRAM), reduces Aβ plaque burden and recuses hippocampal‐dependent cognitive decline in AD‐mouse models. However, the mechanisms underlying the therapeutic benefits of PRAM are not known. Method APP/PS1 mice were treated with PRAM, or saline, chronically via a subcutaneous pump for eight weeks. Additionally, a second subcutaneous pump connected to an ICV cannula delivered an AMYR antagonist, AC187 or aCSF during the last four weeks of peripheral treatment. Radial Arm Water Maze was performed at the end of study to measure spatial memory. Soluble‐Aβ1‐42 hippocampal levels were measured via ELISA and APP processing enzymes were evaluated by Western Blot. Result Preliminary data suggests central blockade of amylin receptors may exacerbate Aβ burden and prevent learning of spatial‐memory tasks; while PRAM treatment showed increased protein expression of certain Aβ degradation enzymes. Conclusion Evaluation of AMYR blockade in AD‐modeled mice has supported a deeper knowledge of amylin signaling in the brain.