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Felipe Rong



Job Title

Research Trainee

Academic Rank




Juliana R. Lopes, Xiaoming Zhang, Felipe Rong, Maria Julia Dalton, Marilia G. Oliveira, Gabriel Pasquarelli, Danielle S. LeServe, Oleg Butovsky, Rafael M. Rezende, Howard L. Weiner

Principal Investigator

Howard L. Weiner

Research Category: Neurosciences


Nasal administration of anti-CD3 monoclonal antibody improves cognition in mouse models of Alzheimer’s disease

Scientific Abstract

Alzheimer’s disease (AD) is a neurodegenerative disorder in which microglial cells change from a homeostatic (M0) to a neurodegenerative (MgnD) phenotype and become activated, contributing to neuroinflammation and cognition decline. We have shown in several mouse models of central nervous system (CNS) inflammation that nasal administration of anti-CD3 monoclonal antibody localizes to the cervical lymph nodes where it induces IL-10-producing Treg cells that migrate to the CNS to control inflammation by switching microglia from MGnD to M0 phenotype. Here, we investigated whether nasal anti-CD3 would improve cognition in APP-PS1 and 3xTg mice, which develop impaired cognition. Nasal anti-CD3 or isotype control were administered at a dose of 1mcg/mouse, 3x/week for 2 months (APP-PS1) or 5 months (3xTg) and then tested for cognition using the Y-maze and the Morris water maze. Mice were then euthanized, and brains removed for microglial cell sorting and RNA-sequencing. We found that nasal anti-CD3 improved short-term memory in APP-PS1 mice and both short- and long-term memory in 3xTg mice. Improvement in cognition was associated with a downregulation of microglial genes associated with neurodegeneration and an upregulation of microglial genes associated with homeostasis. Thus, nasal anti-CD3 may constitute a novel microglial modulating immunotherapy to treat AD.

Lay Abstract

Clinical Implications

Our studies have translational possibilities given that such antibody has been given to healthy volunteers and has shown positive effects in a pilot study of subjects suffering from COVID-19.