{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,14]],"date-time":"2026-09-14T05:05:14Z","timestamp":1789362314181,"version":"build-2803163510"},"reference-count":31,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,9,14]],"date-time":"2026-09-14T00:00:00Z","timestamp":1789344000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:p>Progression in early Parkinson's disease (PD) is heterogeneous, motivating transparent biological markers of group-level progression context. We analyzed longitudinal Parkinson\u2019s Progression Markers Initiative (PPMI) data downloaded on 31 May 2026. The neuroimmune-enriched multibiofluid proteomic index (NEMPI) used 718 quality-control-eligible cerebrospinal fluid and plasma markers, organized into four source-context modules with equal marker and module weights. Direct normalized protein quantification (NPQ) z-standardization was used for the primary reporting implementation, with the log1p implementation examined as a preprocessing sensitivity analysis. Among the 521 participants in the same-sample Cox comparison (173 first observed cognitive-status abnormalities), adding NEMPI to demographic, clinical, alpha-synuclein seed amplification assay, dopamine-transporter imaging, and apolipoprotein E (APOE) epsilon4 covariates yielded an NEMPI hazard ratio (HR) of 1.287 per 1-SD higher value (95% confidence interval (CI): 1.102\u20131.502; P\u00a0=\u00a00.001) and improved likelihood-based fit, but the C-index increment was small (0.0032; bootstrap 95% CI: -0.0093 to 0.0239). The consecutive-abnormality association was stronger but had fewer events, with fewer than 10 events per parameter; the persistent\/irreversible estimate was weaker, and its confidence interval crossed 1. Higher NEMPI was also associated with a modest group-average Montreal Cognitive Assessment (MoCA) and motor trajectory differences, with 5-year translations below published minimal clinically important difference (MCID) ranges. Results were similar under 5-year censoring, discrete-time analysis, stabilized inverse-probability weighting, age analyses, and measured confounder or preanalytic adjustments. NEMPI is therefore interpreted as an abundance-based, neuroimmune-enriched, multibiofluid proteomic composite associated with broad cognitive-motor progression, not as a patient-level prediction tool, clinical threshold, cognition-specific biomarker, or causal mechanism.<\/jats:p>","DOI":"10.3389\/fimmu.2026.1928940","type":"journal-article","created":{"date-parts":[[2026,9,14]],"date-time":"2026-09-14T04:39:04Z","timestamp":1789360744000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["A neuroimmune-enriched multibiofluid proteomic index associated with cognitive-motor progression in early Parkinson\u2019s disease: a longitudinal PPMI cohort study"],"prefix":"10.3389","volume":"17","author":[{"given":"Hao","family":"Wang","sequence":"first","affiliation":[{"name":"The First Affiliated Hospital of Henan University of Science and Technology","place":["Luoyang, China"]},{"name":"Clinical Medical College of Henan University of Science and Technology","place":["Luoyang, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guoqing","family":"Wu","sequence":"additional","affiliation":[{"name":"The First Affiliated Hospital of Henan University of Science and Technology","place":["Luoyang, China"]},{"name":"Clinical Medical College of Henan University of Science and Technology","place":["Luoyang, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dengke","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Neurology Ward 1, Pingdingshan First People\u2019s Hospital","place":["Pingdingshan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wanjun","family":"Feng","sequence":"additional","affiliation":[{"name":"Henan Vocational College of Massage","place":["Luoyang, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xuebin","family":"Zhao","sequence":"additional","affiliation":[{"name":"The First Affiliated Hospital of Henan University of Science and Technology","place":["Luoyang, China"]},{"name":"Clinical Medical College of Henan University of Science and Technology","place":["Luoyang, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Weixiong","family":"Zhang","sequence":"additional","affiliation":[{"name":"The First Affiliated Hospital of Henan University of Science and Technology","place":["Luoyang, China"]},{"name":"Clinical Medical College of Henan University of Science and Technology","place":["Luoyang, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ganqin","family":"Du","sequence":"additional","affiliation":[{"name":"The First Affiliated Hospital of Henan University of Science and Technology","place":["Luoyang, China"]},{"name":"Clinical Medical College of Henan University of Science and Technology","place":["Luoyang, 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