Amyloid Beta – induced leptomeningeal cell JAK/STAT signalling regulates inflammatory responses of astrocytes in Alzheimer’s Disease

The pathological signature of Alzheimer's disease (AD) includes the accumulation of toxic protein aggregates, mainly consisting of amyloid beta (Aβ). Recent strides in fundamental research underscore the pivotal role of waste clearance mechanisms in the brain suggesting it may be an early indication of early-onset AD. This study delves into the involvement of leptomeningeal cells (LMCs), crucial components forming integral barriers within the clearance system, in the context of AD. In this study, we examined the inflammatory responses of LMCs to Aβ, investigating their morphological changes and oxidative responses. The LMCs showed no changes in growth, viability, oxidative stress and vimentin expression in the presence of Aβ. Furthermore, LMCs exhibited a proinflammatory response unique to the Aβ when compared to an LPS control. When treated with JAK/STAT inhibitors, LMCs' inflammatory responses reverted to control levels, suggesting a crucial role of the JAK/STAT pathway in mediating LMC responses to Aβ-induced inflammation. Lastly, Aβ treated LMCs conditioned media demonstrated a reduction in S100B levels in astrocytes compared to both astrocyte control and Aβ-treated astrocytes. This observation suggests a potential anti-inflammatory role of LMCs toward astrocytes, potentially impacting the intricate cellular interplay in AD.