{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T02:19:14Z","timestamp":1791944354794,"version":"4.3.4"},"reference-count":91,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2024,6,8]],"date-time":"2024-06-08T00:00:00Z","timestamp":1717804800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003130","name":"Fonds Wetenschappelijk Onderzoek (FWO)","doi-asserted-by":"publisher","award":["11A2920N"],"award-info":[{"award-number":["11A2920N"]}],"id":[{"id":"10.13039\/501100003130","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003130","name":"Fonds Wetenschappelijk Onderzoek (FWO)","doi-asserted-by":"publisher","award":["11E2423N"],"award-info":[{"award-number":["11E2423N"]}],"id":[{"id":"10.13039\/501100003130","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003130","name":"Fonds Wetenschappelijk Onderzoek (FWO)","doi-asserted-by":"publisher","award":["G042121N"],"award-info":[{"award-number":["G042121N"]}],"id":[{"id":"10.13039\/501100003130","id-type":"DOI","asserted-by":"publisher"}]},{"name":"BAEF","award":["11A2920N"],"award-info":[{"award-number":["11A2920N"]}]},{"name":"BAEF","award":["11E2423N"],"award-info":[{"award-number":["11E2423N"]}]},{"name":"BAEF","award":["G042121N"],"award-info":[{"award-number":["G042121N"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>Microglia activity can drive excessive synaptic loss during the prodromal phase of Alzheimer\u2019s disease (AD) and is associated with lowered cyclic adenosine monophosphate (cAMP) due to cAMP phosphodiesterase 4B (PDE4B). This study aimed to investigate whether long-term inhibition of PDE4B by A33 (3 mg\/kg\/day) can prevent synapse loss and its associated cognitive decline in APPswe\/PS1dE9 mice. This model is characterized by a chimeric mouse\/human APP with the Swedish mutation and human PSEN1 lacking exon 9 (dE9), both under the control of the mouse prion protein promoter. The effects on cognitive function of prolonged A33 treatment from 20 days to 4 months of age, was assessed at 7\u20138 months. PDE4B inhibition significantly improved both the working and spatial memory of APPswe\/PSdE9 mice after treatment ended. At the cellular level, in vitro inhibition of PDE4B induced microglial filopodia formation, suggesting that regulation of PDE4B activity can counteract microglia activation. Further research is needed to investigate if this could prevent microglia from adopting their \u2018disease-associated microglia (DAM)\u2019 phenotype in vivo. These findings support the possibility that PDE4B is a potential target in combating AD pathology and that early intervention using A33 may be a promising treatment strategy for AD.<\/jats:p>","DOI":"10.3390\/cells13121000","type":"journal-article","created":{"date-parts":[[2024,6,10]],"date-time":"2024-06-10T08:49:03Z","timestamp":1718009343000},"page":"1000","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Early Inhibition of Phosphodiesterase 4B (PDE4B) Instills Cognitive Resilience in APPswe\/PS1dE9 Mice"],"prefix":"10.3390","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5756-0082","authenticated-orcid":false,"given":"Ben","family":"Rombaut","sequence":"first","affiliation":[{"name":"Department of Neuroscience, Biomedical Research Institute, Faculty of Medicine and Life Sciences, Hasselt University, 3500 Hasselt, Belgium"},{"name":"Department Psychiatry and Neuropsychology, Mental Health 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