Alzheimer’s disease (AD) is a neurodegenerative disorder characterized by deposition of amyloid plaques in the brain. Amyloid-β (AB) fragments (1-42) are the main components of plaques and are formed by the sequential cleavage of amyloid precursor protein (APP) by β-secretase and ϒ-secretase. Another enzyme, α-secretase, cleaves within the amyloid-β sequence preventing it from aggregating. Previous studies have shown that peripheral administration of a non-aggregating form of the metabolic hormone amylin, an amyloid with similar aggregating properties, improves cognitive function in mouse models of AD and reduces amyloid-β plaque levels. However, how this hormone regulates amyloid-β levels is not known. The purpose of our research was to study the effects of amylin administration on the levels of pro-aggregation soluble amyloid-β fragments (1-42) the expression of α- and β-secretases and the C-terminal fragments that result from enzyme cleavage in the APP/PS1 mouse model of AD. Our data indicate that amylin treatment reduced formic acid-soluble Amyloid-β 1-42 fragments (aggregates). These reductions were paralleled by general upregulation of cleavage enzymes. Taken together, our data demonstrate that amylin may be a potential new therapeutic target for Alzheimer’s disease through its ability to regulate amyloid-beta processing and aggregation.

Keywords: Amylin, Alzheimer’s disease, amyloid-β, APP, α-secretase, β-secretase.