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In Vitro Aggregation Assays Using Hyperphosphorylated Tau Protein
Published on: January 2, 2015
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P-TAU205 IS A BIOMARKER LINKED TO TAU-PET ABNORMALITY: A CROSS-SECTIONAL AND LONGITUDINAL STUDY
Juan Lantero-Rodriguez1, Shorena Janelidze2, Sebastian Palmqvist2,3
1Department of Psychiatry and Neurochemistry, Institute of Neuroscience & Physiology, The Sahlgrenska Academy at the University of Gothenburg, Mölndal, Sweden.
Medrxiv : the Preprint Server for Health Sciences
|November 24, 2025
Summary
Cerebrospinal fluid p-tau205 shows strong links to Alzheimer's disease (AD) progression and cognitive decline. This tau biomarker aids in biological staging and monitoring disease advancement in AD patients.
Area of Science:
- Neuroscience
- Biomarker Discovery
- Alzheimer's Disease Research
Background:
- Current Alzheimer's disease (AD) fluid biomarkers primarily reflect amyloid-β (Aβ) pathology, not tau pathology, which correlates more closely with clinical decline.
- Phosphorylated tau (p-tau) is a key pathological hallmark of AD, and its aggregation is closely linked to neurodegeneration and cognitive impairment.
Purpose of the Study:
- To evaluate cerebrospinal fluid (CSF) phosphorylated tau at epitope 205 (p-tau205) as a biomarker for tau aggregation and disease progression in Alzheimer's disease.
- To assess the association of CSF p-tau205 with established AD biomarkers, neuroimaging, and clinical outcomes across the AD continuum.
Main Methods:
- Analysis of 2,069 CSF samples from the BioFINDER-1 and BioFINDER-2 cohorts, spanning the full AD continuum.
- Measurement of CSF p-tau205 using immunoassays and assessment of cross-sectional and longitudinal associations with amyloid-PET, tau-PET, cortical atrophy, and cognitive scores (MMSE).
- Development of a CSF-based staging model incorporating Aβ42/40, p-tau217, and p-tau205.
Main Results:
- CSF p-tau205 levels were elevated in advanced AD stages and correlated with Aβ-PET, tau-PET, cortical atrophy, and cognitive impairment.
- Baseline CSF p-tau205 predicted future Aβ accumulation and tau-PET uptake, and increased longitudinally, especially in Aβ-positive individuals.
- Longitudinal changes in CSF p-tau205 correlated with cortical thinning and cognitive decline.
- A CSF-based staging model including p-tau205 identified a stage with the highest risk of dementia (HR=6.40).
Conclusions:
- CSF p-tau205 is a robust biomarker reflecting tau aggregation and disease progression in Alzheimer's disease.
- CSF p-tau205 aids in the biological staging of AD and monitoring disease progression, complementing existing biomarkers.
- These findings highlight the utility of CSF p-tau205 for a comprehensive understanding of AD pathophysiology and clinical trajectory.
