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Recent studies have revealed that these synthetic particulates can cross the blood\u2010brain barrier, accelerate amyloid aggregation, impair microglial clearance, hijack the gut\u2010liver\u2010brain axis, and drive neuroinflammation\u2014mechanisms central to neurodegeneration in Alzheimer's and Parkinson's disease. In addition, anionic nanoplastics can induce vascular endothelial leakiness, thereby harboring a paracellular route for their systemic and cerebral access. Yet causality remains unproven in implicating nanoplastics for neurodegeneration in the absence of standardized human exposure data, mechanistic specificity, and epidemiological evidence, especially considering the supra\u2010environmental doses employed. Here, we synthesize current knowledge, examine barriers to causal understanding, and propose a roadmap to advance this emerging scientific frontier of great public concern and inform future strategies for sustainable materials innovation.<\/jats:p>","DOI":"10.1002\/advs.75151","type":"journal-article","created":{"date-parts":[[2026,4,9]],"date-time":"2026-04-09T19:36:07Z","timestamp":1775763367000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Nanoplastics and Neurodegeneration: A Roadmap From Mechanism to Causation"],"prefix":"10.1002","volume":"13","author":[{"given":"Yuhuan","family":"Li","sequence":"first","affiliation":[{"name":"Liver Cancer Institute, Key Laboratory of Carcinogenesis and Cancer Invasion, Zhongshan Hospital, Ministry of Education Fudan University  Shanghai China"},{"name":"Drug Delivery, Disposition and Dynamics, Monash Institute of Pharmaceutical Sciences Monash University  Parkville Victoria Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yue","family":"Wang","sequence":"additional","affiliation":[{"name":"School of Biomedical Sciences and Engineering, Guangzhou International Campus South China University of Technology  Guangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiufang","family":"Liang","sequence":"additional","affiliation":[{"name":"School of Biomedical Sciences and Engineering, Guangzhou International Campus South China University of Technology  Guangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mengze","family":"Xu","sequence":"additional","affiliation":[{"name":"Department of Biology, Faculty of Arts and Sciences Beijing Normal University  Zhuhai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8539-9062","authenticated-orcid":false,"given":"David 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