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Site-Specific Phospho-Tau Aggregation-Based Biomarker Discovery for AD Diagnosis and Differentiation.

Publication ,  Journal Article
Wu, L; Gilyazova, N; Ervin, JF; Wang, S-HJ; Xu, B
Published in: ACS Chem Neurosci
December 7, 2022

Tau aggregates are present in multiple neurodegenerative diseases known as "tauopathies," including Alzheimer's disease (AD), Pick's disease (PiD), progressive supranuclear palsy (PSP), and corticobasal degeneration (CBD). Such misfolded tau aggregates are therefore potential sources for tauopathy biomarker discovery. Using the tau antibody screening approach targeting high-molecular-weight misfolded tau aggregates, we tested several tau antibodies and a comprehensive set of site-specific phospho-tau (p-tau) antibodies targeting tau phosphorylation sites showing high frequencies in AD subjects. Our screens revealed that site-specific p-tau antibodies can not only differentiate AD from non-AD brains, but also discriminate AD from rare tauopathies PiD, PSP, and CBD brains. Differential detection of tau aggregates identified several novel p-tau sites as potential new biomarkers. As a proof-of-principle example, we showed that p-tau198 is a novel promising AD biomarker with sensitivity and specificity comparable with the existing biomarkers p-tau181 and p-tau217. Our results demonstrated that p-tau198 detection can not only differentiate AD from non-AD controls, but also diagnose AD from related 4R tauopathies PSP and CBD with AUCs of 0.96-0.99 (95% CI ranges from 0.90 to 1.00). Promisingly, p-tau198 was able to discriminate mild cognitive impairment from cognitively normal brains with an AUC of 0.75 (95% CI = 0.58-0.92). Our work provides a new avenue for developing diagnosis and differentiation tools for AD and related tauopathies.

Duke Scholars

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Published In

ACS Chem Neurosci

DOI

EISSN

1948-7193

Publication Date

December 7, 2022

Volume

13

Issue

23

Start / End Page

3281 / 3290

Location

United States

Related Subject Headings

  • Humans
  • Biomedical Research
  • Alzheimer Disease
  • 3404 Medicinal and biomolecular chemistry
  • 3401 Analytical chemistry
  • 3101 Biochemistry and cell biology
  • 0304 Medicinal and Biomolecular Chemistry
 

Citation

APA
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MLA
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Wu, L., Gilyazova, N., Ervin, J. F., Wang, S.-H., & Xu, B. (2022). Site-Specific Phospho-Tau Aggregation-Based Biomarker Discovery for AD Diagnosis and Differentiation. ACS Chem Neurosci, 13(23), 3281–3290. https://doi.org/10.1021/acschemneuro.2c00342
Wu, Ling, Nailya Gilyazova, John F. Ervin, Shih-Hsiu J. Wang, and Bin Xu. “Site-Specific Phospho-Tau Aggregation-Based Biomarker Discovery for AD Diagnosis and Differentiation.ACS Chem Neurosci 13, no. 23 (December 7, 2022): 3281–90. https://doi.org/10.1021/acschemneuro.2c00342.
Wu L, Gilyazova N, Ervin JF, Wang S-HJ, Xu B. Site-Specific Phospho-Tau Aggregation-Based Biomarker Discovery for AD Diagnosis and Differentiation. ACS Chem Neurosci. 2022 Dec 7;13(23):3281–90.
Wu, Ling, et al. “Site-Specific Phospho-Tau Aggregation-Based Biomarker Discovery for AD Diagnosis and Differentiation.ACS Chem Neurosci, vol. 13, no. 23, Dec. 2022, pp. 3281–90. Pubmed, doi:10.1021/acschemneuro.2c00342.
Wu L, Gilyazova N, Ervin JF, Wang S-HJ, Xu B. Site-Specific Phospho-Tau Aggregation-Based Biomarker Discovery for AD Diagnosis and Differentiation. ACS Chem Neurosci. 2022 Dec 7;13(23):3281–3290.
Journal cover image

Published In

ACS Chem Neurosci

DOI

EISSN

1948-7193

Publication Date

December 7, 2022

Volume

13

Issue

23

Start / End Page

3281 / 3290

Location

United States

Related Subject Headings

  • Humans
  • Biomedical Research
  • Alzheimer Disease
  • 3404 Medicinal and biomolecular chemistry
  • 3401 Analytical chemistry
  • 3101 Biochemistry and cell biology
  • 0304 Medicinal and Biomolecular Chemistry