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
- differential diagnosis
- neurofilament proteins
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