To interrogate the involvement of PDE4B in the manifestation of AD-related phenotypes, we evaluated the neurocognitive effects of the Pde4bY358C hypomorph in the AppNL-G-F knock-in mouse model [29], which shows Aβ peptide accumulation, neuroinflammation, and cognitive impairment in an age-dependent manner, without the non-physiological overexpression of APP [30]. This evidence concerns the gene APP and Alzheimer disease.