Out-of-control microglia cause cognitive deficits through excessive synaptic elimination in Alzheimer’s Disease

The goal of the research discussed in this thesis was to gain a fundamental understanding of the role of phosphodiesterase (PDE) 4B in microglia, to prevent cognitive deficits in Alzheimer’s disease (AD). We aimed to shed light on both intrinsic and extrinsic regulation of PDE4B to influence various microglial processes. Intrinsic regulation was investigated through the use of knockout models of PDE4B and its chaperone Disrupted-in-Schizophrenia 1 (DISC1), while extrinsic regulation by PDE inhibitors, such as A33, represented the next step in targeting mechanisms that are dysregulated in AD. This thesis describes chapters combining literature search with research employing in vitro assays, combined with in vivo models.