{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,1,16]],"date-time":"2026-01-16T01:44:32Z","timestamp":1768527872553,"version":"3.49.0"},"posted":{"date-parts":[[2025,10,7]]},"group-title":"Neuroscience","reference-count":90,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2025,10,7]],"date-time":"2025-10-07T00:00:00Z","timestamp":1759795200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nd\/4.0\/"}],"funder":[{"name":"National Institute of Health","award":["NIH 1R41ES026225-01"],"award-info":[{"award-number":["NIH 1R41ES026225-01"]}]},{"name":"Western Universtiy of Health Sciences","award":["Intramural grant"],"award-info":[{"award-number":["Intramural grant"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2025,11,22]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                <jats:p>Parkinsonism-Dementia Complex (PDC) is one phenotype of a disappearing neurodegenerative disease (Guam ALS-PDC) that shows clinical and neuropathological relationships with amyotrophic lateral sclerosis (ALS), atypical parkinsonism and Alzheimer\u2019s disease. ALS-PDC has been linked with exposure to environmental factors (notably cycad plant neurotoxins), but evidence from human and animal studies is inconclusive. Patient-derived induced pluripotent stem cells (iPSCs) provide a powerful in vitro system to explore the underlying cause of PDC. iPSC lines were derived from lymphocytes of a PDC-affected Guamanian Chamorro female patient and an age- and gender-matched healthy Chamorro resident of PDC-unaffected Saipan using non-integrating episomal plasmids. iPSCs derived from both patients expressed pluripotency markers (Oct4, SSEA-4, TRA-1-60, Sox2) prior to the generation of neuroprogenitor cells (hNPCs), neurons and astrocytes. An embryoid body protocol was used to derive hNPCs from both iPSC lines while a differentiation media was used to generate neurons from hNPCs. hNPCs derived from both iPSC patients\u2019 lines displayed established neuroprogenitor markers (nestin, Sox2), while the differentiated hNPCs exhibited both neuronal (beta-tubulin III, Map2, doublecortin) and synaptic (synaptophysin, PSD-95) markers. Expression of these protein markers in hNPCs and neurons by dot blotting was also observed for both lines. Astrocyte progenitor cells and mature astrocytes with appropriate markers were also developed from the hNPCs of both lines using commercial kits. Development of these patient-derived iPSCs provides a human model for evaluating the role of environmental (e.g., cycad toxins) and genetic factors in ALS-PDC and possibly other related neurodegenerative diseases.<\/jats:p>","DOI":"10.1101\/2025.10.07.680309","type":"posted-content","created":{"date-parts":[[2025,10,7]],"date-time":"2025-10-07T22:05:12Z","timestamp":1759874712000},"source":"Crossref","is-referenced-by-count":0,"title":["Development of Patient-Derived Neuroprogenitor Cells (hNPCs), Neurons and Astrocytes to Explore the Etiology of Guam Parkinsonism-Dementia Complex (PDC)"],"prefix":"10.64898","author":[{"given":"Anna C.","family":"Chlebowski","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Y.","family":"Yang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nailah 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