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Author Notes:

Correspondence to Dr. Hu: william.hu@emory.edu

Dr. Hu: study concept and design, acquisition of data, analysis and interpretation, statistical analysis, drafting/revision of the manuscript. Ms. Watts, Dr. Grossman, Dr. Glass, Dr. Lah, Dr. Hales, and Mr. Shelnutt: acquisition of data, analysis and interpretation.

Dr. Van Deerlin: acquisition of data, critical revision of the manuscript for important intellectual content. Dr. Trojanowski and Dr. Levey: study concept and design, critical revision of the manuscript for important intellectual content, study supervision.

For all disclosure notes from author, see full record.

Subjects:

Research Funding:

Supported by the Viretta Brady Discovery Fund (Emory University), the Alzheimer's Drug Discovery Foundation/the Association for Frontotemporal Degeneration, and the NIH (AG-25688, AG-10124, AG-17586, and NS-44266).

Drs. Hu, Grossman, and Trojanowski have a patent pending on reduced p/t-Tau ratio as a biomarker for FTLD-TDP.

Keywords:

  • Science & Technology
  • Life Sciences & Biomedicine
  • Clinical Neurology
  • Neurosciences & Neurology
  • FRONTOTEMPORAL LOBAR DEGENERATION
  • PROGRESSIVE SUPRANUCLEAR PALSY
  • HUMAN CEREBROSPINAL-FLUID
  • ALZHEIMERS-DISEASE
  • CLINICOPATHOLOGICAL CORRELATIONS
  • DIAGNOSTIC-CRITERIA
  • DEMENTIA
  • PROGRANULIN
  • EXPRESSION
  • MUTATIONS

Reduced CSF p-Tau(181) to Tau ratio is a biomarker for FTLD-TDP

Tools:

Journal Title:

Neurology

Volume:

Volume 81, Number 22

Publisher:

, Pages 1945-1952

Type of Work:

Article | Final Publisher PDF

Abstract:

Objectives: To validate the ability of candidateCSF biomarkers to distinguish between the 2main forms of frontotemporal lobar degeneration (FTLD), FTLD with TAR DNA-binding protein 43 (TDP-43) inclusions (FTLD-TDP) and FTLD with Tau inclusions (FTLD-Tau). Methods: Antemortem CSF samples were collected from 30 patients with FTLD in a single-center validation cohort, and CSF levels of 5 putative FTLD-TDP biomarkers as well as levels of total Tau (t-Tau) and Tau phosphorylated at threonine 181 (p-Tau181) were measured using independent assays. Biomarkers most associated with FTLD-TDP were then tested in a separate 2-center validation cohort composed of subjects with FTLD-TDP, FTLD-Tau, Alzheimer disease (AD), and cognitively normal subjects. The sensitivity and specificity of FTLD-TDP biomarkers were determined. Results: In the first validation cohort, FTLD-TDP cases had decreased levels of p-Tau181 and interleukin-23, and increased Fas. Reduced ratio of p-Tau181 to t-Tau (p/t-Tau) was the strongest predictor of FTLD-TDP pathology. Analysis in the second validation cohort showed CSF p/t-Tau ratio ,0.37 to distinguish FTLD-TDP from FTLD-Tau, AD, and healthy seniors with 82% sensitivity and 82% specificity. Conclusion: A reduced CSF p/t-Tau ratio represents a reproducible, validated biomarker for FTLD-TDP with performance approaching well-established CSF AD biomarkers. Introducing this biomarker into research and the clinical arena can significantly increase the power of clinical trials targeting abnormal accumulations of TDP-43 or Tau, and select the appropriate patients for target-specific therapies. Classification of evidence: This study provides Class II evidence that the CSF p/t-Tau ratio distinguishes FTLD-TDP from FTLD-Tau. © 2013 American Academy of Neurology.

Copyright information:

© 2013 American Academy of Neurology

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