Joel Shillinglaw, Brian Haner, Kimberly Kerker, Jodi Gresack, Jose Beltran, Herman B Fernandes, Afshin Ghavami, Taleen Hanania
PsychoGenics Inc, Paramus, NJ, USA
The dramatic impact of the class of drugs known as GLP-1
agonists on the treatment and outcomes of patients with diabetes and other
metabolic disorders has spawned interest in other chronic conditions that may
be amenable to these types of interventions. Among these are chronic
neurodegenerative disorders, such as Alzheimer’s disease. Recent literature
reports have suggested that GLP-1 receptor agonists can rescue deficits in
neurotransmission observed in the APP/PS1 mouse model of Alzheimer’s
disease. This double transgenic mouse model overexpresses human forms of
the genes coding for amyloid precursor protein (APP) and Presenilin 1 (PS1),
allowing for study of progressive pathology related to amyloid deposition.
Using this mouse model, we assessed the impact of chronic administration of
the GLP-1 agonists liraglutide and semaglutide on performance in behavioral
memory tasks, synaptic neurotransmission and plasticity (assessed
electrophysiologically in acute brain slices), A-beta isoform levels and
chemokine markers of inflammation.