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Pathological \u03b1-synuclein deposition may commence decades prior to the emergence of cardinal motor symptoms. Long-term investigation of brain and behavioural development in an SNCA-A53T transgenic macaque model offers critical insights into Parkinson\u2019s disease progression.<\/jats:p>\n                  <jats:p>In this study, we systematically characterized SNCA-A53T transgenic rhesus monkeys through multimodal assessments. Our results showed that these transgenic monkeys exhibited phosphorylated \u03b1-synuclein aggregation patterns and dopaminergic degeneration resembling Parkinson\u2019s disease patients. Progressive motor and cognitive deficits were observed in transgenic monkeys with ageing. Polysomnographic analysis revealed rapid eye movement sleep behaviour disorder manifestations in transgenic animals. Four-year longitudinal MRI tracking demonstrated abnormal developmental patterns of cortical surface area alongside alterations in thickness and volume. The single-cell transcriptome revealed that astrocyte-specific gene dysregulation and cell loss contribute to brain atrophy in transgenic monkeys. Cortical and subcortical grey matter regions showing volume reduction were functionally associated with behavioural deficits and differentiated transgenic animals from wild-type controls.<\/jats:p>\n                  <jats:p>Collectively, this comprehensive study provides evidence that SNCA-A53T transgenic monkeys recapitulate Parkinson\u2019s disease pathophysiology while demonstrating the utility of longitudinal monitoring in genetically engineered non-human primates for tracking neurodegenerative disease progression.<\/jats:p>","DOI":"10.1093\/brain\/awag046","type":"journal-article","created":{"date-parts":[[2026,2,5]],"date-time":"2026-02-05T12:38:54Z","timestamp":1770295134000},"page":"3134-3149","source":"Crossref","is-referenced-by-count":0,"title":["\u03b1-Synuclein aggregation and brain atrophy in\n                    <i>SNCA<\/i>\n                    -A53T transgenic monkeys are correlated with parkinsonism"],"prefix":"10.1093","volume":"149","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7528-4034","authenticated-orcid":false,"given":"Jingkuan","family":"Wei","sequence":"first","affiliation":[{"name":"State Key Laboratory of Primate Biomedical Research, Institute of Primate Translational Medicine, Kunming University of Science and Technology , Kunming, Yunnan 650500 ,","place":["China"]},{"name":"Yunnan Key Laboratory of Primate Biomedical Research , Kunming, Yunnan 650500 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shulin","family":"Li","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Primate Biomedical Research, Institute of Primate Translational Medicine, Kunming University of Science and Technology , Kunming, Yunnan 650500 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dingna","family":"Duan","sequence":"additional","affiliation":[{"name":"Department of Radiology and BRIC, University of North Carolina at Chapel Hill , Chapel Hill, NC 27599 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kunhua","family":"Wu","sequence":"additional","affiliation":[{"name":"Department of MRI, The First People\u2019s Hospital of Yunnan Province, The Affiliated Hospital of Kunming University of Science and Technology , Kunming, Yunnan 650032 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xu","family":"Liu","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Primate Biomedical Research, Institute of Primate Translational Medicine, Kunming University of Science and Technology , Kunming, Yunnan 650500 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ran","family":"Zhu","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Primate Biomedical Research, Institute of Primate Translational Medicine, Kunming University of Science and 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Translational Medicine, Kunming University of Science and Technology , Kunming, Yunnan 650500 ,","place":["China"]},{"name":"Yunnan Key Laboratory of Primate Biomedical Research , Kunming, Yunnan 650500 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yongchang","family":"Chen","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Primate Biomedical Research, Institute of Primate Translational Medicine, Kunming University of Science and Technology , Kunming, Yunnan 650500 ,","place":["China"]},{"name":"Yunnan Key Laboratory of Primate Biomedical Research , Kunming, Yunnan 650500 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shaoxing","family":"Dai","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Primate Biomedical Research, Institute of Primate Translational Medicine, Kunming University of Science and Technology , Kunming, Yunnan 650500 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