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OBJECTIVE To see whether the distribution patterns of phosphorylated 43kDa TAR DNA-binding protein (pTDP-43) intraneuronal inclusions in amyotrophic lateral sclerosis (ALS) permit recognition of neuropathological stages. METHODS pTDP-43 immunohistochemistry was performed on 70 μm sections from ALS autopsy cases (N = 76) classified by clinical phenotype(More)
C9ORF72-hexanucleotide repeat expansions and ubiquilin-2 (UBQLN2) mutations are recently identified genetic markers in amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration (FTLD). We investigate the relationship between C9ORF72 expansions and the clinical phenotype and neuropathology of ALS and FTLD. Genetic analysis and(More)
Clinically isolated syndrome (CIS) represents the earliest phase of multiple sclerosis (MS). This study tested whether biomarkers for axonal degeneration can improve upon sensitivity and specificity of magnetic resonance imaging (MRI) parameters in predicting conversion from CIS to MS. Patients with CIS (n = 52), relapsing-remitting MS (RRMS, n = 38) and(More)
While cognitive deficits are increasingly recognized as common symptoms in amyotrophic lateral sclerosis (ALS), the underlying histopathologic basis for this is not known, nor has the relevance of neuroinflammatory mechanisms and microglial activation to cognitive impairment (CI) in ALS been systematically analyzed. Staining for neurodegenerative disease(More)
Cerebrovascular disease and vascular risk factors are associated with Alzheimer's disease, but the evidence for their association with other neurodegenerative disorders is limited. Therefore, we compared the prevalence of cerebrovascular disease, vascular pathology and vascular risk factors in a wide range of neurodegenerative diseases and correlate them(More)
OBJECTIVE To test whether biomarkers for axonal degeneration correlated with clinical subtypes and were of use in predicting progression of ALS. METHODS Patients with ALS (n = 69), patients with Alzheimer disease (AD; n = 73), and age-matched controls (n = 33) were included in this prospective study. CSF levels of tau protein and neurofilaments (NfHSMI35)(More)
Cerebrospinal fluid (CSF) proteins may provide important information about the pathomechanisms present in multiple sclerosis (MS). Although diagnostic criteria for early MS are available, there is still a need for biomarkers, predicting disease subtype and progression to improve individually tailored treatment. Using the two-dimensional difference gel(More)
We used two-dimensional difference in-gel electrophoresis (2-D-DIGE) for proteome analysis of cerebrospinal fluid (CSF) in Guillain-Barré syndrome (GBS). Spots showing >2-fold difference between GBS and controls were analysed using MALDI-TOF mass spectrometry. Proteins that were up-regulated in GBS included haptoglobin, serine/threonine kinase 10,(More)
Erythropoietin (EPO) and its specific receptor (EPOR) have been proposed to act as an endogenous system protecting against neuronal injury and neurodegeneration. We measured EPO in cerebrospinal fluid (CSF) of patients with neurodegenerative diseases, and tested for a correlation with an established biomarker of neuro-axonal damage, tau protein. Patients(More)
Amyotrophic lateral sclerosis (ALS) is a progressive and seriously disabling adult-onset neurological disease. Ninety percent of ALS patients are sporadic cases (sALS) with no clear genetic linkage. Accumulating evidence indicates that various microRNAs (miRNAs), expressed in a spatially and temporally controlled manner in the brain, play a key role in(More)