{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,10]],"date-time":"2026-06-10T14:28:56Z","timestamp":1781101736849,"version":"3.54.1"},"reference-count":23,"publisher":"SAGE Publications","issue":"2","license":[{"start":{"date-parts":[[2023,7,18]],"date-time":"2023-07-18T00:00:00Z","timestamp":1689638400000},"content-version":"unspecified","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JAD"],"published-print":{"date-parts":[[2023,7,18]]},"abstract":"<jats:p>Background: Retromer complex proteins are decreased in postmortem brain tissues from Down syndrome subjects and inversely correlate with the Alzheimer\u2019s disease-like neuropathology. However, whether targeting in vivo the retromer system affects cognitive deficits and synaptic function in Down syndrome remains unknown. Objective: The aim of the current study was to examine the effects of pharmacological retromer stabilization on cognitive and synaptic functions in a mouse model of Down syndrome. Methods: Ts65dn mice were administered the pharmacological chaperone, TPT-172, or vehicle from 4 to 9 months of age and then assessed for changes in cognitive function. To assess the effects of TPT-172 on synaptic plasticity, hippocampal slices from Ts65dn mice were incubated in TPT-172 and used for field potential recordings. Results: Chronic TPT-172 treatment improved performance in cognitive function tests, its incubation with hippocampal slices ameliorated synaptic function response. Conclusion: Pharmacological stabilization of the retromer complex improves synaptic plasticity and memory in a mouse model of Down syndrome. These results support the therapeutic potential of pharmacological retromer stabilization for individual with Down syndrome.<\/jats:p>","DOI":"10.3233\/jad-230205","type":"journal-article","created":{"date-parts":[[2023,6,13]],"date-time":"2023-06-13T10:24:36Z","timestamp":1686651876000},"page":"513-518","source":"Crossref","is-referenced-by-count":4,"title":["Retromer Stabilization Improves Cognitive Function and Synaptic Plasticity in a Mouse Model of Down Syndrome"],"prefix":"10.1177","volume":"94","author":[{"given":"Mary Elizabeth","family":"Curtis","sequence":"first","affiliation":[{"name":"Alzheimer\u2019s Center at Temple, Lewis Katz School of Medicine, Temple University, Philadelphia, PA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tiffany","family":"Smith","sequence":"additional","affiliation":[{"name":"Alzheimer\u2019s Center at Temple, Lewis Katz School of Medicine, Temple University, Philadelphia, PA, 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