Neurofilaments and tau proteins in cerebrospinal fluid and serum in dementias and neuroinflammation.

Lenka Fialova,Jana Svarcova,Ales Bartos

doi:10.5507/bp.2017.038

Abstract

The aim of this study was to evaluate the diagnostic potential of cerebrospinal fluid (CSF) and serum levels of neurocytoskeletal proteins and their ratios for the diagnosis of dementias and to assess the differences in neurocytoskeletal proteins between neurodegeneration and neuroinflammation. CSF and serum levels of neurofilament light subunits (NFL) and neurofilament heavy subunits (NFH) as well as CSF levels of total tau (t-tau) and phosphorylated tau (p-tau) proteins were determined using ELISA in 20 Alzheimer's disease patients (AD group), 13 patients with other dementias (OD group), 17 patients with inflammatory aseptic neuro-infections (IP), and 20 aged-matched cognitively normal elderly persons (NC group). The ratio CSF p-tau/t-tau was significantly higher in the NC group than that in the AD or OD groups (P<0.0005 for each group). The CSF NFH/p-tau and CSF NFL/p-tau ratios were significantly lower in AD patients than OD patients (P≤0.003). Serum and CSF NFL and CSF NFH levels were significantly higher in OD patients than AD patients (P≤0.03). The lowest values of the CSF NFL/NFH ratio were found in the IP group and they significantly differed from those in normal controls (P<0.0001) and any dementia group (IP vs. AD P<0.0001; IP vs. OD P=0.03). CSF tau proteins and their index differentiated between AD or OD patients and cognitively normal subjects, while CSF levels of neurofilaments expressed as their index seem to contribute to the discrimination between patients with neuroinflammation and normal controls or AD patients.

Highlights

Alzheimer’s disease (AD) is characterized by specific neuropathological features involving the formation of beta-amyloid plaques and the presence of neurofibrillary tangles (NFT) in the brain[1,2]
Mini-Mental State Examination (MMSE) score and ACE-R-CZ score were lower in AD and other dementias than in normal controls (P≤0.0001 for each comparison) and inflammatory patients (MMSE: P
Neurocytoskeletal protein levels in cerebrospinal fluid (CSF) and serum The levels of neurofilament light subunits (NFL) in CSF differ among the groups (Fig. 1A)

Summary

Introduction

Alzheimer’s disease (AD) is characterized by specific neuropathological features involving the formation of beta-amyloid plaques and the presence of neurofibrillary tangles (NFT) in the brain[1,2]. The presence of beta-amyloid plaques and NFT are reflected in the altered levels of beta-amyloid, phosphorylated tau protein (p-tau) and total tau protein (t-tau) in CSF (further referred to as a CSF triplet), and less specific processes like axonal damage by altered neurofilament (NF) levels[4,5,6]. Determination of these proteins facilitates differentiation of patients with AD from cognitively normal elderly individuals and other dementias[7,8,9]. Higher NF levels in CSF have been found in other dementias, and determination of NFL and NFH may be valuable in the differentiation of dementias[5,19,20]

Methods

Results

Conclusion