CSF neurofilament proteins in the differential diagnosis of dementia

Abstract

<b>Background:</b> Neurofilament (NF) proteins are major cytoskeletal constituents of neurons. Increased CSF NF levels may reflect neuronal degeneration. <b>Objective:</b> 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’s disease (EAD; onset ⩽65 years of age), and in elderly dementia patients between dementia with Lewy bodies (DLB) and late onset AD (LAD; onset &gt;65 years of age). <b>Methods:</b> In CSF of 28 FTLD, 37 EAD, 18 DLB and 33 LAD patients, and 26 control subjects, we analysed NF light chain (NFL), phosphorylated NF heavy chain (pNFH), amyloid β₄₂ protein (Aβ₄₂), total tau and tau phosphorylated at threonine 181 (p-tau₁₈₁). <b>Results:</b> CSF NFL levels were higher in FTLD patients compared with EAD patients (p&lt;0.001), and diagnostic accuracy of p-tau₁₈₁ and Aβ₄₂ analysis improved with addition of NFL analysis (sensitivity 86%, specificity 100%). CSF pNFH levels were elevated in DLB, LAD and FTLD compared with controls (p&lt;0.05) but no significant differences were found between the dementia groups. <b>Conclusions:</b> In the diagnostic workup of relatively young dementia patients, CSF NFL levels may play a role in the discrimination between FTLD and EAD, especially in combination with Aβ₄₂ and p-tau₁₈₁ analysis.