ABSTRACT
BACKGROUND: Tau protein has been proposed as biomarker of axonal damage leading to irreversible neurological impairment in MS. CSF concentrations may be useful when determining risk of progression from ON to MS. OBJECTIVE: To investigate the association between tau protein concentration and 14-3-3 protein in the cerebrospinal fluid (CSF) of patients with monosymptomatic optic neuritis (ON) versus patients with monosymptomatic onset who progressed to multiple sclerosis (MS). To evaluate results against data found in a complete literature review. METHODS: A total of 66 patients with MS and/or ON from the Department of Neurology of Glostrup Hospital, University of Copenhagen, Denmark, were included. CSF samples were analysed for tau protein and 14-3-3 protein, and clinical and paraclinical information was obtained from medical records. RESULTS: The study shows a significantly increased concentration of tau protein in CSF from patients with relapsing-remitting MS and patients monosymptomatic at onset who progressed to MS, but interestingly no increased tau protein concentration in monosymptomatic ON. The concentration of tau protein was significantly correlated to Expanded Disability Status Scale score. No 14-3-3 protein was detected in any CSF sample. CONCLUSIONS: The results of this study invite further exploration of the possible role of tau protein as a prognostic factor to predict progression from ON to MS in future studies.
Subject(s)
Brain/metabolism , Multiple Sclerosis/cerebrospinal fluid , Optic Neuritis/cerebrospinal fluid , tau Proteins/cerebrospinal fluid , 14-3-3 Proteins/cerebrospinal fluid , Adult , Biomarkers/cerebrospinal fluid , Denmark , Disability Evaluation , Disease Progression , Female , Hospitals, University , Humans , Male , Middle Aged , Multiple Sclerosis/diagnosis , Optic Neuritis/diagnosis , Prognosis , Severity of Illness Index , Time Factors , Up-Regulation , Young AdultABSTRACT
BACKGROUND: Mutations in the Presenilin 2 gene (PSEN2) are rare causes of Alzheimer's disease (AD). Pathogenic mutations in the genes associated with autosomal dominant inherited AD have been shown to alter processing of the amyloid precursor protein (APP) resulting in a relative increase of the amount of Abeta42 peptide. METHODS AND RESULTS: We present a patient with neuropathologically confirmed early-onset AD characterized by profound language impairment. The patient was heterozygous for a novel missense mutation in exon 11 of the PSEN2 gene leading to a predicted amino acid substitution from valine to methionine in position 393, a conserved residue. However, in vitro expression of PSEN2 V393M cDNA did not result in detectable increase of the secreted Abeta42/40 peptide ratio. The mutation was not found in 384 control individuals tested. CONCLUSIONS: The possible pathogenic nature of the mutation is not clarified. We discuss the limitations of functional PSEN2 studies and the challenges associated with genetic counselling of family members at risk.
