Modulating Neutrophil JAK/STAT Pathways: Impacts on Brain Anatomy in an Alzheimer's Disease Model

Presenters/Authors(s)

Andrew Tiu, Jacob Feldmann, Aminata Coulibaly

Abstract or Description

Alzheimer's disease (AD) is a progressive, neurodegenerative disorder which affects cognition, behavior, and memory. The 3xTg mouse model is crucial to studying the mechanisms and progression of AD. This model mimics key AD features by mutations in the amyloid precursor proteins (APP), presenilin-1 (PSEN1), and microtubule associated protein tau (MAPT) genes. Changes to several regions of the brain have been linked to AD, such as enlarged ventricles and overall decrease in brain volume and cortical thickness due to loss of gray matter. Neutrophils are a type of immune cell that play a key role in the inflammatory response. While it has been established that neutrophils have been found to be in the brain during AD, their exact mechanisms and contributions to AD pathology still remain unclear. The JAK/STAT pathway is a cellular signaling mechanism that regulates immune cell recruitment and function, including neutrophils. Control and AD mouse models are treated with JAK/STAT signaling modulators via bone marrow transplantation. Novel Magnetic Resonance Imagining (MRI) techniques allow the volumes of the affected brain regions to be delineated and tracked throughout the disease progression. Understanding JAK/STAT’s role could allow insight into how neutrophil activity influences the progression of Alzheimer’s disease.