{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,4]],"date-time":"2026-09-04T17:49:22Z","timestamp":1788544162853,"version":"build-2803163510"},"reference-count":42,"publisher":"SAGE Publications","issue":"2","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JAD"],"published-print":{"date-parts":[[2023,7,18]]},"abstract":"<jats:p>Background: Down syndrome (DS) is caused by an extra copy of all or part of chromosome 21. The patients with DS develop typical Alzheimer\u2019s disease (AD) neuropathology, indicating the role of genes on human chromosome 21 (HSA21) in the pathogenesis of AD. Purkinje cell protein 4 (PCP4), also known as brain-specific protein 19, is a critical gene located on HSA21. However, the role of PCP4 in DS and AD pathogenesis is not clear. Objective: To explore the role of PCP4 in amyloid-\u03b2 protein precursor (A\u03b2PP) processing in AD. Methods: In this study, we investigated the role of PCP4 in AD progression in vitro and in vivo. In vitro experiments, we overexpressed PCP4 in human Swedish mutant A\u03b2PP stable expression or neural cell lines. In vitro experiments, APP23\/PS45 double transgenic mice were selected and treated with AAV-PCP4. Multiple topics were detected by western blot, RT-PCR, immunohistochemical and behavioral test. Results: We found that PCP4 expression was altered in AD. PCP4 was overexpressed in APP23\/PS45 transgenic mice and PCP4 affected the processing of A\u03b2PP. The production of amyloid-\u03b2 protein (A\u03b2) was also promoted by PCP4. The upregulation of endogenous A\u03b2PP expression and the downregulation of ADAM10 were due to the transcriptional regulation of PCP4. In addition, PCP4 increased A\u03b2 deposition and neural plaque formation in the brain, and exuberated learning and memory impairment in transgenic AD model mice. Conclusion: Our finding reveals that PCP4 contributes to the pathogenesis of AD by affecting A\u03b2PP processing and suggests PCP4 as a novel therapeutic target for AD by targeting A\u03b2 pathology.<\/jats:p>","DOI":"10.3233\/jad-230192","type":"journal-article","created":{"date-parts":[[2023,6,9]],"date-time":"2023-06-09T10:19:12Z","timestamp":1686305952000},"page":"737-750","source":"Crossref","is-referenced-by-count":11,"title":["PCP4 Promotes Alzheimer\u2019s Disease Pathogenesis by Affecting Amyloid-\u03b2 Protein Precursor Processing"],"prefix":"10.1177","volume":"94","author":[{"given":"Dongjie","family":"Hu","sequence":"first","affiliation":[{"name":"Chongqing Key Laboratory of Translational Medical Research in Cognitive Development and Learning and Memory Disorders, Ministry of Education Key Laboratory of Child Development and Disorders, National Clinical Research Center for Child Health and Disorders, China International Science and Technology Cooperation Base of Child Development and Critical Disorders, Children\u2019s Hospital of Chongqing Medical University, Chongqing, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiangjun","family":"Dong","sequence":"additional","affiliation":[{"name":"Chongqing Key Laboratory of Translational Medical Research in Cognitive Development and Learning and Memory Disorders, Ministry of Education Key Laboratory of Child Development and Disorders, National Clinical Research Center for Child Health and Disorders, China International Science and Technology Cooperation Base of Child Development and Critical Disorders, Children\u2019s Hospital of Chongqing Medical University, Chongqing, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qunxian","family":"Wang","sequence":"additional","affiliation":[{"name":"Chongqing Key Laboratory of Translational Medical Research in Cognitive Development and Learning and Memory Disorders, Ministry of Education Key Laboratory of Child Development and Disorders, National Clinical Research Center for Child Health and Disorders, China International Science and Technology Cooperation Base of Child Development and Critical Disorders, Children\u2019s Hospital of Chongqing Medical University, Chongqing, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mingjing","family":"Liu","sequence":"additional","affiliation":[{"name":"Chongqing Key Laboratory of Translational Medical Research in Cognitive Development and Learning and Memory Disorders, Ministry of Education Key Laboratory of Child Development and Disorders, National Clinical Research Center for Child Health and Disorders, China International Science and Technology Cooperation Base of Child Development and Critical Disorders, Children\u2019s Hospital of Chongqing Medical University, Chongqing, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuyue","family":"Luo","sequence":"additional","affiliation":[{"name":"Chongqing Key Laboratory of Translational Medical Research in Cognitive Development and Learning and Memory Disorders, Ministry of Education Key Laboratory of Child Development and Disorders, National Clinical Research Center for Child Health and Disorders, China International Science and Technology Cooperation Base of Child Development and Critical Disorders, Children\u2019s Hospital of Chongqing Medical University, Chongqing, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zijun","family":"Meng","sequence":"additional","affiliation":[{"name":"Chongqing Key Laboratory of Translational Medical Research in Cognitive Development and Learning and Memory Disorders, Ministry of Education Key Laboratory of Child Development and Disorders, National Clinical Research Center for Child Health and Disorders, China International Science and Technology Cooperation Base of Child Development and Critical Disorders, Children\u2019s Hospital of Chongqing Medical University, Chongqing, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zijuan","family":"Feng","sequence":"additional","affiliation":[{"name":"Chongqing Key Laboratory of Translational Medical Research in Cognitive Development and Learning and Memory Disorders, Ministry of Education Key Laboratory of Child Development and Disorders, National Clinical Research Center for Child Health and Disorders, China International Science and Technology Cooperation Base of Child Development and Critical Disorders, Children\u2019s Hospital of Chongqing Medical University, Chongqing, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Weihui","family":"Zhou","sequence":"additional","affiliation":[{"name":"Chongqing Key Laboratory of Translational Medical Research in Cognitive Development and Learning and Memory Disorders, Ministry of Education Key Laboratory of Child Development and Disorders, National Clinical Research Center for Child Health and Disorders, China International Science and Technology Cooperation Base of Child Development and Critical Disorders, Children\u2019s Hospital of Chongqing Medical University, Chongqing, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9928-889X","authenticated-orcid":false,"given":"Weihong","family":"Song","sequence":"additional","affiliation":[{"name":"Chongqing Key Laboratory of Translational Medical Research in Cognitive Development and Learning and Memory Disorders, Ministry of Education Key Laboratory of Child Development and Disorders, National Clinical Research Center for Child Health and Disorders, China International Science and Technology Cooperation Base of Child Development and Critical Disorders, Children\u2019s Hospital of Chongqing Medical University, Chongqing, China"},{"name":"Institute of Aging, Key Laboratory of Alzheimer\u2019s Disease of Zhejiang Province, Zhejiang Provincial Clinical Research Center for Mental Disorders, School of Mental 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