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This study examined astrocytic contributions to neuropsychiatric symptoms (NPS), focusing on astrocytic protein activity and its relationship with NPS severity, accounting for clinical and pathological features of NDs.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>METHODS<\/jats:title>\n                    <jats:p>Cerebrospinal astrocytic proteins (glial fibrillary acidic protein [GFAP], chitinase\u20103\u2010like protein 1 [YKL\u201040], and aquaporin\u20104 [AQP4]) from Alzheimer's Disease Neuroimaging Initiative (ADNI) (AD) and Parkinson's Progression Markers Initiative (PPMI) (PD) were analyzed using K\u2010means clustering. Six NPS domains, ND\u2010specific pathologies (amyloid\u2010beta\/A\u03b2\u00a0for AD, alpha\u2010synuclein\/\u03b1Syn for PD), and nonspecific pathology (phosphorylated tau\/ptau) were assessed.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>RESULTS<\/jats:title>\n                    <jats:p>In both samples, three astrocytic clusters were identified, and the \u201chighYKL|lowOthers\u201d cluster (high YKL\u201040, low GFAP\/AQP4) consistently showed lower ptau and NPS severity compared to the \u201chighAll\u201d cluster (high GFAP, YKL\u201040, AQP4). In PPMI, the \u201chighYKL|lowOthers\u201d cluster also attenuated the relationship between \u03b1Syn and NPS compared to the \u201chighAll\u201d cluster.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>DISCUSSION<\/jats:title>\n                    <jats:p>Astrocytic activity relates to NPS, highlighting astrocytic proteins as potential therapeutic targets for NPS in NDs.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Highlights<\/jats:title>\n                    <jats:p>\n                      <jats:list list-type=\"bullet\">\n                        <jats:list-item>\n                          <jats:p>Astrocytic protein clusters were linked to NPS severity in AD and PD cohorts.<\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>The \u201chighYKL|lowOthers\u201d cluster showed lower ptau and NPS severity than \u201callhigh\u201d cluster in AD and PD cohorts.<\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>Astrocytic proteins may serve as therapeutic targets for managing NPS in NDs.<\/jats:p>\n                        <\/jats:list-item>\n                      <\/jats:list>\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/alz.70242","type":"journal-article","created":{"date-parts":[[2025,5,20]],"date-time":"2025-05-20T05:52:36Z","timestamp":1747720356000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Relationships between neuropsychiatric symptoms, subtypes of astrocyte activities, and brain pathologies in Alzheimer's disease and Parkinson's disease"],"prefix":"10.1002","volume":"21","author":[{"ORCID":"https:\/\/orcid.org\/0009-0005-0298-4052","authenticated-orcid":false,"given":"Oceanna Yueran","family":"Li","sequence":"first","affiliation":[{"name":"CogT Lab Department of Psychiatry and Behavioral Sciences Stanford University  Stanford California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Steven","family":"Shin","sequence":"additional","affiliation":[{"name":"CogT Lab Department of Psychiatry and Behavioral Sciences Stanford University  Stanford California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sa","family":"Zhou","sequence":"additional","affiliation":[{"name":"CogT Lab Department of Psychiatry and Behavioral Sciences Stanford University  Stanford California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adam","family":"Turnbull","sequence":"additional","affiliation":[{"name":"CogT Lab Department of Psychiatry and Behavioral Sciences Stanford University  Stanford California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1945-0362","authenticated-orcid":false,"given":"F. 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