Effect of Passive Amylin Immunotherapy on Amylin and AB Plaque Burden in AD

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Abstract Alzheimer’s disease (AD) is a progressive form of neurodegenerative disorder in the elderly population; approved therapy aims at reducing cerebral amyloid ß (Aß) lesions. There is accumulating evidence from different research teams (including ours) showing that amyloid-forming amylin secreted from the pancreas forms mixed deposits with Aß in the brain microvasculature and brain parenchyma, in both familial and sporadic forms of AD. To describe how circulating amyloid-forming amylin affects brain function and Aß pathology, we used both AD and non-AD rats transgenic for human amylin in the pancreas (rat amylin is non-amyloidogenic). Our results show: 1, either pancreatic hypersecretion or intravenous injection of human amylin in APP/PS1 rats exacerbates AD-like pathology through cerebrovascular amylin deposition and amylin-Aß cross-seeding; 2, genetically suppressed amylin secretion in APP/PS1 rats decreases cerebral amylin–Aß plaque formation. These results suggest the hypothesis that passive immunotherapy against circulating amyloid-forming amylin can reduce cerebrovascular amylin deposition amylin-Aß cross-seeding in plaques. To test this hypothesis and uncover cellular and molecular mechanisms whereby lower amyloid-forming amylin protects against brain Aß deposition, we will use polyclonal anti-amylin antibodies that we generated in rabbits and APP/PS1 mice with “tunable” conditional reduced or enhanced human amylin expression in the pancreatic ß-cells.
Effective start/end date6/1/245/31/26


  • Alzheimers Association: $139,912.00


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