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CSF neurofilament light differs in neurodegenerative diseases and predicts severity and survival
Tobias Skillbäck1, Bahman Farahmand2, Jonathan W Bartlett2
1From the Clinical Neurochemistry Laboratory (T.S., C.R., N.M., K.B., H.Z.), Institute of Neuroscience and Physiology, Department of Neurochemistry, the Sahlgrenska Academy at the University of Gothenburg, Mölndal; Division of Clinical Geriatrics, Department of Neurobiology, Care Sciences, and Society (B.F., D.R., B.W., M.E.), and KI Alzheimer Disease Research Center (A.W.), Karolinska Institutet, Stockholm; Department of Geriatric Medicine (B.F., D.R., M.E.), Karolinska University Hospital, Stockholm, Sweden; Centre for Statistical Methodology (J.W.B.), London School of Hygiene & Tropical Medicine, London, UK; Department of Veterans Affairs Medical Center (N.M.), Center for Imaging of Neurodegenerative Diseases, San Francisco, CA; Clinical Memory Research Unit (K.N.), Department of Clinical Sciences Malmö, Lund University, Malmö; Department of Public Health and Caring Sciences/Geriatrics (L.K.), Uppsala University; Institute of Neuroscience and Physiology (L.R.), Department of Neurology, the Sahlgrenska Academy at the University of Gothenburg, Sweden; and UCL Institute of Neurology (J.M.S., H.Z.), Queen Square, London, UK. tobias.skillback@neuro.gu.se.
Objectives:
We hypothesized that CSF neurofilament light (NFL) levels would be elevated in dementias with subcortical involvement, including vascular dementia (VaD), but less elevated in dementias primarily affecting gray matter structures, such as Alzheimer disease (AD), and that elevated CSF NFL would correlate with disease severity and shorter survival time irrespective of clinical diagnosis.
Methods:
We included 3,356 individuals with dementia who had CSF NFL analyzed in our laboratory between 2005 and 2012. Clinical diagnoses and Mini-Mental State Examination (MMSE) scores were obtained from the Swedish Dementia Registry, and in selected cases (n = 478), date of death from the Swedish Mortality Registry.
Results:
CSF NFL differed among clinical diagnoses, with the highest levels seen in frontotemporal dementia, VaD, and mixed AD and VaD. Early-onset AD (younger than 65 years) had the lowest levels. High CSF NFL correlated with low MMSE score and short survival time irrespective of diagnosis, and was also particularly evident in AD.
Conclusions:
CSF NFL differs among different neurodegenerative diseases and is especially high in dementias engaging subcortical brain regions, such as VaD and mixed AD and VaD, but also in frontotemporal dementia. The association of high CSF NFL levels with disease severity and short survival supports the notion that high CSF NFL levels indicate more aggressive disease processes.
