{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"medRxiv"}],"indexed":{"date-parts":[[2026,1,16]],"date-time":"2026-01-16T13:04:16Z","timestamp":1768568656477,"version":"3.49.0"},"posted":{"date-parts":[[2025,10,22]]},"group-title":"Neurology","reference-count":40,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2025,10,22]],"date-time":"2025-10-22T00:00:00Z","timestamp":1761091200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2025,10,22]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                <jats:p>Current fluid biomarkers for Alzheimer\u2019s disease (AD) track amyloid-\u03b2 (A\u03b2) pathology more strongly than tau, even though clinical and cognitive decline relate more closely to tau. We evaluated cerebrospinal fluid (CSF) phosphorylated tau at epitope 205 (p-tau205), measured using immunoassays, as a biomarker of tau aggregation. A total of 2,069 samples from the BioFINDER-2 (n=1,364) and BioFINDER-1 (n=705) cohorts spanning the full AD continuum were analyzed to assess cross-sectional and longitudinal associations with imaging and clinical measures. CSF p-tau205 levels were elevated in both biologically and clinically advanced disease stages. In A\u03b2-positive individuals, cross-sectional p-tau205 correlated with A\u03b2-PET (R\u00b2=0.26), tau-PET (R\u00b2=0.29), cortical atrophy (R\u00b2=0.14) and cognition (MMSE, R\u00b2=0.14). Baseline p-tau205 predicted subsequent A\u03b2 accumulation (R\u00b2=0.44) and tau-PET uptake (R\u00b2=0.33), and increased more steeply over time in A\u03b2-positive than A\u03b2-negative participants (\u03b2[95%CI]=0.16[0.12\u20130.21], p&lt;0.001). Longitudinal p-tau205 change related to cortical thinning (R\u00b2=0.32) and cognitive decline (R\u00b2\u22650.41). Incorporating A\u03b242\/40, p-tau217 and p-tau205 into a CSF-based staging model, the final p-tau205-positive stage showed the strongest cortical atrophy, cognitive impairment, and risk of incident dementia (HR=6.40[4.28\u20139.59]). These findings support CSF p-tau205 as a valuable marker for biological staging and progression monitoring in AD.<\/jats:p>","DOI":"10.1101\/2025.10.21.25338437","type":"posted-content","created":{"date-parts":[[2025,10,22]],"date-time":"2025-10-22T19:15:15Z","timestamp":1761160515000},"source":"Crossref","is-referenced-by-count":0,"title":["P-TAU205 IS A BIOMARKER LINKED TO TAU-PET ABNORMALITY: A CROSS-SECTIONAL AND LONGITUDINAL STUDY"],"prefix":"10.64898","author":[{"given":"Juan","family":"Lantero-Rodriguez","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shorena","family":"Janelidze","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sebastian","family":"Palmqvist","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Luisa 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