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Cerebrospinal fluid biomarkers predict frontotemporal dementia trajectory
Peter A Ljubenkov1, Adam M Staffaroni1, Julio C Rojas1
1Department of Neurology Memory and Aging Center University of California, San Francisco San Francisco California.
Annals of Clinical and Translational Neurology
|October 24, 2018
Summary
High cerebrospinal fluid neurofilament light chain (NfL) indicates more aggressive frontotemporal dementia (FTD). Other biomarkers like total tau, phosphorylated tau (p-tau181), and amyloid beta (Aβ42) also predict disease progression in FTD subtypes.
Area of Science:
- Neuroscience
- Biomarker Research
- Neurology
Background:
- Frontotemporal dementia (FTD) encompasses several progressive neurodegenerative disorders.
- Accurate prognostic markers are crucial for managing FTD subtypes, including behavioral variant FTD (bvFTD), semantic variant PPA (svPPA), and nonfluent variant PPA (nfvPPA).
Purpose of the Study:
- To evaluate the prognostic value of cerebrospinal fluid (CSF) biomarkers: neurofilament light chain (NfL), total tau (t-tau), phosphorylated tau (p-tau181), and amyloid beta (Aβ42) in distinct FTD subtypes.
- To determine the predictive capacity of these biomarkers for clinical and radiographic changes over time.
Main Methods:
- A cohort study comparing 49 controls with 40 bvFTD, 24 svPPA, and 26 nfvPPA patients.
- Baseline CSF biomarkers were analyzed using linear mixed effect models to predict yearly clinical and radiographic changes over multiple follow-up visits.
Main Results:
- Elevated CSF NfL levels were associated with faster clinical worsening and frontotemporal degeneration (reduced volume and fractional anisotropy) in bvFTD and nfvPPA.
- High t-tau predicted faster progression in nfvPPA. In bvFTD, higher p-tau181 and lower Aβ42 predicted faster clinical progression and frontotemporal degeneration, respectively.
- NfL and p-tau181 showed greater predictive value in patients with tau pathology compared to TDP-43 pathology.
Conclusions:
- Elevated CSF NfL is a significant predictor of more aggressive disease course in bvFTD and nfvPPA.
- CSF t-tau, p-tau181, and Aβ42 also offer prognostic value for specific measures of disease aggressiveness across FTD subtypes.
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