Year: 2026
Type: article
Study design: Observational Study
Abstract: Among soluble tau biomarkers, tau phosphorylation at position T205 (p-tau205) has been suggested to distinctly emergence across Alzheimer’s disease (AD) continuum compared to other p-tau and non-phosphorylated tau forms, and a moderate relationship with both amyloid-β and tau aggregated pathologies. To evaluate this and further expand the characterization of this biomarker, we measured cerebrospinal fluid (CSF) p-tau205 using an in-house developed immunoassay in a total of 2069 samples from the BioFINDER-2 ( n = 1364) and BioFINDER-1 ( n = 705) cohorts. These two cohorts spanned the full AD continuum and 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 Aβ-positive individuals, baseline p-tau205 levels correlated with Aβ-PET (R² = 0.28), tau-PET (medial temporal: R 2 = 0.35, neocortical: R² = 0.29), cortical atrophy (R² = 0.15) and cognition (MMSE, R² = 0.15). Baseline p-tau205 predicted subsequent Aβ accumulation (R² = 0.44) and tau-accumulation measured by PET (R² = 0.33). Longitudinal p-tau205 levels increased more steeply longitudinally in Aβ-positive than Aβ-negative participants (β[95%CI] = 0.16[0.12–0.21], p < 0.001). Longitudinal p-tau205 changes were associated with cortical thinning (R² = 0.32) and cognitive decline (R² ≥ 0.41). When incorporating Aβ42/40, p-tau217 and p-tau205 into a conceptual CSF-based staging model, the final p-tau205-positive stage showed the strongest association with cortical atrophy, cognitive impairment, and risk of progression to dementia (HR = 6.40[4.28–9.59]). These findings support CSF p-tau205 as a biomarker of Alzheimer’s disease pathology and progression with potential value for biological staging.
Source: Molecular Psychiatry
Institutions: University of Gothenburg, Lund University, Skåne University Hospital, University of Wisconsin–Madison, Sahlgrenska University Hospital, UK Dementia Research Institute, National Hospital for Neurology and Neurosurgery, UCL Queen Square Institute of Neurology, University College London, Indian Institute of Science Bangalore, Hospital de Sant Pau, Institut de Recerca Sant Pau, Pasqual Maragall Foundation, Barcelonaβeta Brain Research Center, Hospital del Mar Research Institute
Language: English
Subfield: Psychiatry and Mental health
Field: Medicine
Domain: Health Sciences
Open Access status: hybrid
Estimated APC paid: $5,490
Funders: Alzheimer's Association, Alzheimer's Drug Discovery Foundation, BrightFocus Foundation, Familjen Erling-Perssons Stiftelse, Cure Alzheimer's Fund, Stiftelsen för Gamla Tjänarinnor, Australian Government, National Institute for Health and Care Research, University College London, European Commission, Lunds Universitet, Hjärnfonden, Knut och Alice Wallenbergs Stiftelse, Vetenskapsrådet, Göteborgs Universitet, Konung Gustaf V:s och Drottning Victorias Frimurarestiftelse, Alzheimerfonden, Skånes universitetssjukhus, UK Dementia Research Institute, Stiftelsen Bundy Academy, Parkinsonfonden, HORIZON EUROPE Framework Programme
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OpenAlex ID: W7204473317