Ante mortem cerebrospinal fluid tau levels correlate with postmortem tau pathology in frontotemporal lobar degeneration
Open accessAbstract
Objective: To test the hypotheses that (1) antemortem cerebrospinal fluid (CSF) tau levels correlate with postmortem tau pathology in frontotemporal lobar degeneration (FTLD) and (2) tauopathy patients have higher phosphorylated‐tau levels compared to transactivation response element DNA‐binding protein 43 (TDP‐43) proteinopathy patients while accounting for Alzheimer's disease (AD) copathology. Methods: Patients had autopsy‐confirmed FTLD with tauopathy (n = 31), TDP‐43 proteinopathy (n = 49), or AD (n = 26) with antemortem CSF. CSF tau levels were compared between groups and correlated with digital histology measurement of postmortem tau pathology averaged from three cerebral regions (angular gyrus, mid‐frontal cortex, and anterior cingulate gyrus). Multivariate linear regression tested the association of ante mortem CSF tau levels with postmortem tau pathology adjusting for demographics. Results: Multivariate regression found an independent association of ante mortem CSF phosphorylated tau levels with postmortem cerebral tau pathology in FTLD (Beta = 1.3; 95% confidence interval = 0.2‐2.4; p < 0.02). After excluding patients with coincident AD‐associated tau pathology accompanying sporadic FTLD, we found lower CSF phosphorylated tau levels in the TDP‐43 group (median = 7.4pg/ml; interquartile range [IQR] = 6.0, 12.3; n = 26) compared to the tauopathy group (median = 12.5pg/ml; IQR = 10.7, 15.0; n = 23; Z = 2.6; p < 0.01). Interpretation: CSF phosphorylated‐tau levels are positively associated with cerebral tau burden in FTLD. In vivo detection of AD copathology in sporadic FTLD patients may help stratify clinical cohorts with pure neuropathology in which low CSF phosphorylated‐tau levels may have diagnostic utility to distinguish TDP‐43 proteinopathy from tauopathy. Autopsy‐confirmed samples are critical for FTLD biomarker development and validation. Ann Neurol 2017;82:247–258
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Both t-tau and NfL may be useful for the diagnosis and prognosis of FTLD.
“The combination of CSF t-tau and NfL discriminated between early onset AD and FTLD, 9 and both analytes may be useful for the diagnosis and prognosis of FTLD.1,[10][11][12]”
From Plasma Tau and Neurofilament Light in Frontotemporal Lobar Degeneration and Alzheimer Disease (2021) · cites this paper as [10]
The Introduction (page unavailable) reports possible diagnostic utility for a CSF p-tau-to-t-tau ratio in distinguishing FTLD subtypes, which offers limited support for a role for t-tau. The Results and Discussion assess diagnostic accuracy for p-tau, not t-tau alone. Our copy does not establish diagnostic or prognostic utility for NfL, or prognostic utility for t-tau. (LLM, conf=0.82)
Experimental — accuracy not yet measuredThe value of CSF tau measurements is limited to pure cases of FTLD (e.g., without copathologies).
“Other studies have shown that the value of CSF tau measurements is limited to pure cases of FTLD (e.g., without copathologies).”
From New developments of biofluid‐based biomarkers for routine diagnosis and disease trajectories in frontotemporal dementia (2022) · cites this paper as [61]
The performance of CSF p-tau181 to discriminate between FTD pathological subtypes (FTLD-tau vs. FTLD-TDP) was considerably reduced when mutation carriers were analyzed separately (AUCs of 0.87 in sporadic pure cases vs. 0.58 in genetic cases).
“the performance of CSF p‐tau181 to discriminate between FTD pathological subtypes (i.e., FTLD‐tau vs. FTLD‐TDP) was considerably reduced when mutation carriers were analyzed separately (AUCs of 0.87 in sporadic pure cases vs. 0.58 in genetic cases). 61 , 67”
From New developments of biofluid‐based biomarkers for routine diagnosis and disease trajectories in frontotemporal dementia (2022) · cites this paper as [61]
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- Authors
- Irwin, D. J., Lleó, A., Xie, S. X., McMillan, C. T., Wolk, D. A., Lee, E. B., Van Deerlin, V. M., Shaw, L. M., Trojanowski, J. Q., & Grossman, M.
- Affiliations
- University of Pennsylvania (US)
- Hospital de Sant Pau (ES)
- Center for Neurodegenerative Disease Research Department of Pathology and Laboratory Medicine, University of Pennsylvania Perelman School of Medicine Philadelphia PA
- Corresponding author
- Irwin, David J.
- ORCID
- Venue
- Annals of Neurology
- Publisher
- Wiley
- Published
- 2017-08
- Volume
- 82
- Issue
- 2
- Pages
- 247-258
- ISSN
- 0364-5134 (ISSN-L)
- 1531-8249
- PMC
- PMC5776747
- OpenAlex
- W2739360812
- Cited by
- 67
- References
- 49
- Citations by year
- 2026: 3 · 2025: 1 · 2024: 5 · 2023: 6 · 2022: 19 · 2021: 9 · 2020: 5 · 2019: 7 · 2018: 8 · 2017: 4
- FWCI
- 4.86
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Annals of Neurology (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institute of Neurological Disorders and Stroke
- NIH (AG038490, AG010124, NS053488, AG032953, AG017586, AG043503, NS088341)
- Wyncote Foundation
- Topics
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Health Sciences › Medicine › Neurology › Amyotrophic Lateral Sclerosis Research
- Keywords
- frontotemporal lobar degeneration, tauopathy, TDP-43 proteinopathy, cerebrospinal fluid tau, phosphorylated tau, biomarkers, differential diagnosis, digital histology
- MeSH terms
- Aged, Alzheimer Disease, Female, Frontal Lobe, Gyrus Cinguli, Humans, Male, Middle Aged, Parietal Lobe, Phosphorylation, Biomarkers, Case-Control Studies, tau Proteins, Tauopathies, Frontotemporal Lobar Degeneration, TDP-43 Proteinopathies
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Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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