Protective effect of PDE4B subtype-specific inhibition in an App knock-in mouse model for Alzheimer's disease.

ABSTRACT: Meta-analysis of genome-wide association study data has implicated PDE4B in the pathogenesis of Alzheimer's disease (AD), the leading cause of senile dementia. PDE4B encodes one of four subtypes of cyclic adenosine monophosphate (cAMP)-specific phosphodiesterase-4 (PDE4A-D). To interrogate the involvement of PDE4B in the manifestation of AD-related phenotypes, the effects of a hypomorphic mutation (Pde4b^Y358C) that decreases PDE4B's cAMP hydrolytic activity were evaluated in the App^NL-G-F knock-in mouse model of AD using the Barnes maze test of spatial memory, ¹⁴C-2-deoxyglucose autoradiography, thioflavin-S staining of β-amyloid (Aβ) plaques, and inflammatory marker assay and transcriptomic analysis (RNA sequencing) of cerebral cortical tissue. At 12 month

SUBMITTER: Armstrong P 

PROVIDER: S-EPMC11319650 | biostudies-literature | 2024 Sep

REPOSITORIES: biostudies-literature