AUTHOR=Fella Eleni , Papacharalambous Revekka , Kynigopoulos Demos , Ioannou Maria , Derua Rita , Christodoulou Christiana , Stylianou Myrto , Karaiskos Christos , Kagiava Alexia , Petroula Gerasimou , Pierides Chryso , Kyriakou Maria , Koumas Laura , Costeas Paul , Panayiotou Elena TITLE=Pharmacological activation of the C5a receptor leads to stimulation of the β-adrenergic receptor and alleviates cognitive impairment in a murine model of familial Alzheimer’s disease JOURNAL=Frontiers in Immunology VOLUME=13 YEAR=2022 URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2022.947071 DOI=10.3389/fimmu.2022.947071 ISSN=1664-3224 ABSTRACT=

Alzheimer’s disease (AD) is a progressive neurodegenerative disease of the brain causing either familial or sporadic dementia. We have previously administered the modified C5a receptor agonist (EP67) for a short period to a transgenic mouse model of AD (5XFAD) and have observed not only reduction in β-amyloid deposition and gliosis but also improvement in cognitive impairment. Inquiring, however, on the effects of EP67 in an already heavily burdened animal, thus representing a more realistic scenario, we treated 6-month-old 5XFAD mice for a period of 14 weeks. We recorded a significant decrease in both fibrillar and pre-fibrillar β-amyloid as well as remarkable amelioration of cognitive impairment. Following proteomic analysis and pathway association, we postulate that these events are triggered through the upregulation of β-adrenergic and GABAergic signaling. In summary, our results reveal how inflammatory responses can be employed in inducing tangible phenotype improvements even in advanced stages of AD.