{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,22]],"date-time":"2026-10-22T16:06:29Z","timestamp":1792685189768,"version":"4.5.0"},"reference-count":54,"publisher":"SAGE Publications","issue":"4","license":[{"start":{"date-parts":[[2025,10,29]],"date-time":"2025-10-29T00:00:00Z","timestamp":1761696000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"},{"start":{"date-parts":[[2025,10,29]],"date-time":"2025-10-29T00:00:00Z","timestamp":1761696000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"funder":[{"DOI":"10.13039\/501100000024","name":"Canadian Institutes of Health Research","doi-asserted-by":"publisher","award":["MOP 74465"],"award-info":[{"award-number":["MOP 74465"]}],"id":[{"id":"10.13039\/501100000024","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000038","name":"Natural Sciences and Engineering Research Council of Canada","doi-asserted-by":"publisher","award":["402594-11 and 16-05171"],"award-info":[{"award-number":["402594-11 and 16-05171"]}],"id":[{"id":"10.13039\/501100000038","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Journal of Alzheimer\u2019s Disease"],"published-print":{"date-parts":[[2025,12]]},"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>The abnormal extracellular accumulation of amyloid-\u03b2 (A\u03b2) plaques and intracellular tau inclusions are hallmarks of early events in the pathogenesis of Alzheimer's disease (AD). Although growing evidence implicates neurotransmitter dysregulation in AD-associated neurodegeneration, the influence of these pathological hallmarks on dopaminergic signaling remains poorly understood. This study reports changes in dopamine receptor (DR), A\u03b2, and astrocyte distribution in the cortex and hippocampus of 5XFAD mice.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>To investigate how A\u03b2 pathology alters dopamine receptor subtype expression in the AD brain and neuronal models, and whether this contributes to tau phosphorylation and CDK5 activation.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      We examined DR1-DR5 expression and localization in the cortex and hippocampus of 5XFAD mice using immunohistochemistry, qPCR, and western blot. SH-SY5Y cells were differentiated with retinoic acid and treated with A\u03b2\n                      <jats:sub>1\u221242<\/jats:sub>\n                      ; MC-65 cells produced endogenous A\u03b2 via tetracycline withdrawal. DR1, DR2, and DR3 agonists were used to assess effects on cAMP, CDK5, and tau phosphorylation.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>In AD brains, Gs-coupled DR1 and DR5 were upregulated, while Gi-coupled DR2, DR3, and DR4 were downregulated at mRNA and protein levels. SH-SY5Y and MC-65 cells recapitulated these subtype-specific changes following A\u03b2 exposure. In the cortex, receptor alterations were implicated in increased CDK5 and tau phosphorylation. DR activation modulated cAMP and kinase pathways in a receptor- and cell-specific manner. The cortex showed greater vulnerability to A\u03b2-associated degeneration, whereas the hippocampus was more susceptible to inflammation and tau pathology.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>These findings reveal a role for DR subtypes in regulating tau phosphorylation and CDK5, with implications for AD-related cognitive dysfunction.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1177\/13872877251389961","type":"journal-article","created":{"date-parts":[[2025,10,29]],"date-time":"2025-10-29T16:54:55Z","timestamp":1761756895000},"page":"1696-1716","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":1,"title":["Brain region-specific dopamine receptor changes and astrocyte activation influence tau pathology through CDK5 in Alzheimer's disease models"],"prefix":"10.1177","volume":"108","author":[{"given":"Sneha","family":"Singh","sequence":"first","affiliation":[{"name":"Faculty of Pharmaceutical Sciences, The University of British Columbia, Vancouver, BC, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ujendra","family":"Kumar","sequence":"additional","affiliation":[{"name":"Faculty of Pharmaceutical Sciences, The University of British Columbia, Vancouver, BC, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"179","published-online":{"date-parts":[[2025,10,29]]},"reference":[{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1201\/9781003602477"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1001\/jamaneurol.2013.5847"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(15)01124-1"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1007\/s12035-024-04333-y"},{"key":"e_1_3_3_6_2","article-title":"Changes in neurotransmitter-related functional connectivity along the Alzheimer's disease continuum","volume":"7","author":"Manca R","year":"2025","unstructured":"Manca R, De Marco M, Soininen H, et al. 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