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While symptomatic treatment is available for motor symptoms of PD, non\u2010motor complications such as dementia result in diminished life quality for patients and are far more difficult to treat. In this study, we analyzed PD\u2010associated alterations in the hippocampus of PD patients, since this brain region is strongly affected by PD dementia. We focused on synapses, analyzing the proteome of post\u2010mortal hippocampal tissue from 16 PD cases and 14 control subjects by mass spectrometry. Whole tissue lysates and synaptosomal fractions were analyzed in parallel. Differential analysis combined with bioinformatic network analyses identified neuronal pentraxin 1 (NPTX1) to be significantly dysregulated in PD and interacting with proteins of the synaptic compartment. Modulation of NPTX1 protein levels in primary hippocampal neuron cultures validated its role in synapse morphology. Our analysis suggests that NPTX1 contributes to synaptic pathology in late\u2010stage PD and represents a putative target for novel therapeutic strategies.<jats:boxed-text content-type=\"graphic\" position=\"anchor\"><jats:graphic xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" mimetype=\"image\/png\" position=\"anchor\" specific-use=\"enlarged-web-image\" xlink:href=\"graphic\/jnc15924-fig-0004-m.png\"><jats:alt-text>image<\/jats:alt-text><\/jats:graphic><\/jats:boxed-text><\/jats:p>","DOI":"10.1111\/jnc.15924","type":"journal-article","created":{"date-parts":[[2023,7,29]],"date-time":"2023-07-29T06:31:06Z","timestamp":1690612266000},"page":"862-874","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["Proteomic analysis of the human hippocampus identifies neuronal pentraxin 1 (<scp>NPTX1<\/scp>) as synapto\u2010axonal target in late\u2010stage Parkinson's 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