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CSF neurofilament proteins in the differential diagnosis of dementia
  1. D de Jong (d.dejong{at}neuro.umcn.nl)
  1. Radboud University Nijmegen Medical Centre, Netherlands
    1. R W.M.M. Jansen (r.jansen{at}ger.umcn.nl)
    1. Radboud University Nijmegen Medical Centre, Netherlands
      1. Y A.L. Pijnenburg (y.pijnenburg{at}vumc.nl)
      1. VU University Medical Centre, Amsterdam, Netherlands
        1. W J.A. van Geel (w.vangeel{at}cukz.umcn.nl)
        1. Radboud University Nijmegen Medical Centre, Netherlands
          1. G F. Borm (g.borm{at}epib.umcn.nl)
          1. Radboud University Nijmegen Medical Centre, Netherlands
            1. B P.H. Kremer (h.kremer{at}neuro.umcn.nl)
            1. Radboud University Nijmegen Medical Centre, Netherlands
              1. M M. Verbeek (m.verbeek{at}cukz.umcn.nl)
              1. Radboud University Nijmegen Medical Centre, Netherlands

                Abstract

                Background: Neurofilament (NF) proteins are major cytoskeletal constituents of neurons. Increased CSF NF levels may reflect neuronal degeneration. Objective: To investigate the diagnostic value of CSF NF analysis to discriminate in relatively young dementia patients between frontotemporal lobe degeneration (FTLD) and early-onset Alzheimer disease (EAD; onset ≤ 65 years of age), and in elderly dementia patients between dementia with Lewy bodies (DLB) and late-onset AD (LAD; onset > 65 years of age).

                Methods: In CSF of 28 FTLD (mean age 63.2 & [plusmn] 9.1 years), 37 EAD (61.2 ± 4.5 years), 18 DLB (72.3 ± 8.5 years), and 33 LAD patients (75.6 ± 4.2 years), and 26 control subjects (60.9 ± 7.2 years), we analysed NF light chain (NFL), phosphorylated NF heavy chain (pNFH), amyloid & [beta]42 protein (Aβ42), total tau (t-tau), and tau phosphorylated at threonine 181 (p-tau181).

                Results: CSF NFL levels were significantly higher in FTLD patients (20.6 ± 18.0 pg/ml) compared to EAD patients (8.5 ± 8.2 pg/ml), and diagnostic accuracy improved in combination with CSF levels of p- tau181 and Aβ42 (sensitivity 86%, specificity 100%). CSF pNFH levels were significantly elevated in DLB (182 ± 151 pg/ml), LAD (157 ± 102 pg/ml), and FTLD (142 ± 90 pg/ml) compared to controls (79 ± 20 pg/ml), however, no significant differences were found between the dementia groups.

                Conclusions: In the diagnostic workup of relatively young dementia patients, CSF NFL levels may play a role in de discrimination between FTLD and EAD, especially in combination with Aβ42 and p-tau181 analysis.

                • alzheimer disease
                • cerebrospinal fluid
                • dementia
                • differential diagnosis
                • neurofilament proteins

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