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Updated: Feb 5, 2026
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In Vitro Aggregation Assays Using Hyperphosphorylated Tau Protein
Published on: January 2, 2015
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Phosphorylated peptide Tau-pT181 induced tau aggregation and cognitive dysfunction.
1Department of Pathophysiology, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
Journal of Alzheimer'S Disease : JAD
|February 3, 2026
Summary
Phosphorylation of Tau protein at threonine 181 (p-Tau181) directly causes Tau aggregation, leading to synaptic damage, cognitive impairment, and neuronal loss in Alzheimer's disease (AD). This finding supports p-Tau181 as a key diagnostic marker and therapeutic target for AD.
Area of Science:
- Neuroscience
- Biochemistry
- Molecular Biology
Background:
- Phosphorylation of Tau protein at threonine 181 (p-Tau181) is a critical biomarker for Alzheimer's disease (AD) detection.
- The precise mechanisms linking Tau phosphorylation at Thr181 to Tau aggregation and neuropathology are not fully understood.
Purpose of the Study:
- To investigate the impact of the phosphorylated Tau peptide at Thr181 (Tau-pT181) on Tau aggregation, synaptic function, and cognitive abilities.
- To elucidate the role of Tau-pT181 in neuropathological changes associated with AD.
Main Methods:
- Synthesis of Tau-pT181 and non-phosphorylated Tau peptide (Tau-nT181).
- Assessment of Tau aggregation using Thioflavin S assay and in cell models (293/tau cells).
- Evaluation of synaptic protein levels in primary hippocampal neurons and cognitive function in rats following peptide injection.
- Transcriptome analysis of iPSC-derived neurons treated with Tau-pT181/Tau-nT181.
Main Results:
- Tau-pT181 significantly promoted R3 peptide aggregation, unlike Tau-nT181.
- Tau-pT181 induced Tau aggregation in 293/tau cells and reduced synapse-associated proteins in neurons.
- Intracerebral injection of Tau-pT181 in rats led to endogenous Tau aggregation, synaptic damage, neuronal loss, and significant cognitive impairment.
- Transcriptome analysis revealed Tau-pT181 impacts axonogenesis, neuronal development, and Wnt signaling.
Conclusions:
- This study provides the first direct evidence that Tau phosphorylation at Thr181 drives Tau aggregation.
- Tau-pT181 directly causes neuropathological alterations and cognitive deficits, establishing its role in AD pathogenesis.
- The findings support the Tau Thr181 phosphorylation site as a crucial diagnostic marker and potential therapeutic target for AD.
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