Csf p-tau181/tau ratio as biomarker for TDP pathology in frontotemporal dementia
Abstract
Our objective was to evaluate the CSF phospho-Tau181/total-Tau (p/t-Tau) ratio to distinguish between the two main forms of frontotemporal lobar degeneration (FTLD): FTLD with TDP-43 (FTLD-TDP) and FTLD with Tau inclusions (FTLD-Tau). CSF p/t-Tau ratio was examined in 79 FTLD patients with predictable neuropathology, i.e. Tau (affected by progressive supranuclear palsy or carriers of mutations within the MAPT gene) or TDP-43 (carriers of mutations within granulin, C9orf72, TARDBP genes or affected by FTD with motor neuron disease). FTLD patients were randomly grouped in a training cohort (n = 39) to assess the best CSF p/t-Tau cut-off score according to ROC analysis, and a validation cohort (n = 40) to evaluate accuracy values of the identified marker. Results showed that, in the training cohort, we found a significantly reduced CSF p/t-Tau ratio in FTLD-TDP relative to FTLD-Tau. ROC analysis for p/t-Tau ratio was 0.873 and cut-off score of 0.136 allowed to differentiate FTLD-TDP and FTLD-Tau with 81.8% sensitivity and 88.2% specificity, respectively. Analysis in the validation cohort showed CSF p/t-Tau ratio < 0.136 to distinguish FTLD-TDP from FTLD-Tau with 83.3% specificity and 63.6% sensitivity, respectively. The positive predictive value of detecting TDP neuropathology was 82.4%. In conclusion, a reduced CSF p/t-Tau ratio represents a viable biomarker to correctly identify TDP pathology in FTLD.
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CSF p-tau/t-tau ratio demarcates FTD-TDP patients from FTD-tau cases with sensitivity and specificity values around 82% and 62%, respectively.
“Several independent studies have shown that CSF p‐tau/t‐tau ratio demarcate FTD‐TDP patients from FTD‐tau cases with sensitivity and specificity values around 82% and 62%, respectively.”
From New developments of biofluid‐based biomarkers for routine diagnosis and disease trajectories in frontotemporal dementia (2022) · cites this paper as [94]
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- Authors
- Borroni, B., Benussi, A., Archetti, S., Galimberti, D., Parnetti, L., Nacmias, B., Sorbi, S., Scarpini, E., & Padovani, A.
- Affiliations
- University of Brescia (IT)
- Azienda Socio Sanitaria Territoriale degli Spedali Civili di Brescia (IT)
- University of Milan (IT)
- University of Perugia (IT)
- University of Florence (IT)
- Corresponding author
- Borroni, Barbara
- ORCID
- Venue
- Amyotrophic Lateral Sclerosis and Frontotemporal Degeneration
- Publisher
- Informa UK Limited
- Published
- 2014-10-29
- Volume
- 16
- Issue
- 1-2
- Pages
- 86-91
- ISSN
- 2167-8421 (ISSN-L)
- 2167-9223
- OpenAlex
- W1973874272
- Cited by
- 77
- References
- 34
- Citations by year
- 2026: 3 · 2025: 3 · 2024: 5 · 2023: 5 · 2022: 14 · 2021: 7 · 2020: 6 · 2019: 9 · 2018: 8 · 2017: 9 · 2016: 5 · 2015: 3
- FWCI
- 3.70
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Amyotrophic Lateral Sclerosis and Frontotemporal Degeneration (publishedVersion)
- PubMed (publishedVersion)
- ArTS Archivio della ricerca di Trieste (University of Trieste https://www.units.it/) (submittedVersion)
- Florence Research (University of Florence) (submittedVersion)
- Institutional Research Information System (Università degli Studi di Brescia) (submittedVersion)
- Topics
- Health Sciences › Medicine › Neurology › Amyotrophic Lateral Sclerosis Research
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Keywords
- cerebrospinal fluid biomarkers, frontotemporal lobar degeneration, FTLD-TDP, FTLD-tau, TDP-43 pathology, tau pathology, differential diagnosis, progressive supranuclear palsy, MAPT mutations, C9orf72, TARDBP
- MeSH terms
- Aged, Aged, 80 and over, DNA-Binding Proteins, Enzyme-Linked Immunosorbent Assay, Female, Humans, Italy, Male, Middle Aged, Peptide Fragments, Phosphorylation, Cohort Studies, Amyloid beta-Peptides, tau Proteins, Frontotemporal Dementia
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