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Background Unlike antibodies against amyloid-β, little is known about serum antibodies to neuron-specific cytoskeletal proteins in patients with Alzheimer's disease (AD). Objective We aimed to study IgG autoantibodies against tau protein, light (NFL) and heavy subunits (NFH) of neurofilaments in serum of AD patients and elderly controls and to explore the evolution of antineurocytoskeletal antibody levels over time. Methods Antibodies against three targets (tau, NFL, and NFH) were measured using ELISA in 100 serum samples from 51 cognitively normal elderly controls and 49 patients with AD. Our primary cross-sectional design was further extended to monitor fluctuations over 1-2 years in a subset of individuals. Results The AD patients had lower levels of anti-tau antibodies (p = 0.03) and even lower anti-NFH antibodies (p = 0.005) than those in the control group at baseline. On the contrary, anti-NFL antibodies or total IgG concentrations in serum did not differ. All three antibodies remained stable in both groups except for a selective and significant anti-tau decline in AD patients (p = 0.03). Conclusions The different responses to these antigens suggest some antibody selectivity in AD. The significant decline was observed for only serum anti-tau antibodies in AD patients over time and it corresponds to lower anti-tau levels in these patients. Our findings indicate a special feature of disease-relevant antigens and humoral autoimmunity in AD.

Heavy neurofilaments (NFH) released from neurons during axonal injury induce a humoral immune response. We measured CSF and serum levels of NFH proteins and anti-NFH IgG antibodies in 19 patients with clinically isolated syndrome (CIS) converting to multiple sclerosis, in 20 stable CIS patients, 23 patients with multiple sclerosis (MS) and 32 control subjects using ELISA. CSF and intrathecal levels and CSF/serum ratios of anti-NFH antibodies were increased in the CIS patients early developing MS while NFH protein concentrations were similar among the groups. Changes associated with NFH are more pronounced for antibodies than for protein itself and may aid in prediction of CIS patients.

The aim of the study was to investigate genetic and biochemical background of PAPP-A (pregnancy-associated plasma protein A) in patients with risk pregnancies.Five PAPP-A gene polymorphisms and PAPP-A maternal serum levels were studied together in 165 women in third trimester pregnancies complicated with threatening preterm labor (n=98), preeclampsia (n=35), intrauterine growth restriction (n=34) and ICP (intrahepatic cholestasis of pregnancy) (n=15). 114 healthy pregnant women served as controls.Preeclamptic patients had significantly higher frequency of TT genotype of Cys327Cys polymorphism compared to controls (p0.01). Patients with ICP had increased serum levels of PAPP-A compared to controls and correlation analysis showed significant relationship between PAPP-A and CRP (C-reactive protein) in the patients with intrauterine growth restriction (r=0.49, p=0.007).Our study indicates the association of TT genotype of Cys327Cys polymorphism of the PAPP-A gene with preeclampsia. However, further study with larger groups of preeclamptic patients is needed to confirm our results.

Background: The aim of the study was to assess autoimmune involvement in amyotrophic lateral sclerosis (ALS). Methods: We measured IgG antibodies against light (NFL) and medium (NFM) subunits of neurofilaments using ELISA in paired cerebrospinal fluid (CSF) and serum samples from 38 ALS patients and 20 controls. Results: Serum levels of anti-NFL were higher in ALS patients than in controls (P

A release of light neurofilament subunits (NFL) into cerebrospinal fluid (CSF) and serum in multiple sclerosis (MS) may induce an immune response. We examined CSF and serum NFL levels and IgG antibodies against NFL in 19 patients with a clinically isolated syndrome (CIS) early converted into MS, 20 CIS-non-converters, 23 MS patients and 32 controls. CSF NFL levels were significantly higher in all patient groups. The highest CSF or intrathecally (IT) synthesized anti-NFL antibodies and CSF/serum ratios of anti-NFL antibodies were observed in CIS-converters. CSF NFL and CSF or IT anti-NFL antibodies could be surrogate biomarkers of axonal injury in early MS.

states. The optimalprocess of clinical assessmentmay includemultiple technologies such as neuropsychological assessment, neuroimaging, and fluid biomarker analysis, each used at appropriate time points in a staged diagnostic pathway. EDAR is a Europe-wide prospective longitudinal study assessing the potential for CSF and other biomarkers, including cognition, in the early diagnosis of AD. Methods: Patients with mild cognitive impairment, AD and other dementias and healthy elderly controls (total n 1⁄4 144) were recruited from seven centres across Europe. Memory, attention and executive functions were assessed using the Cambridge Neuropsychological Test Battery (CANTAB). Cerebrospinal fluid was obtained on a single occasion and assayed using Luminex for As1-42, total tau and hyperphosphorylated tau. Results: Lower CSF As1-42 levels were associated with poorer performance on CANTAB paired associates learning (rho1⁄4 -.3, p< .001) and spatial working memory (rho1⁄4-.3, p1⁄4 .002) tests, andwith slower (rho1⁄4-.3, p1⁄4 .001) andmore variable (rho1⁄4-.4, p< .001) choice reaction time. The tau:As1-42 ratiowas lower in individuals with better episodic memory and less variable choice reaction time (both rho 1⁄4 .2, p 1⁄4 .01). High P-tau181P levels were associated with faster simple reaction time (rho 1⁄4 -.3, p 1⁄4 .001). CSF biomarker levels appeared unrelated to scores on tests of semantic memory and executive function. Associations between cognitive and CSF biomarkers differed between diagnostic groups. Conclusions: Among healthy and impaired elderly individuals, scores on computerised cognitive tests are correlated with CSF biomarkers of amyloid and tau pathologies.

Antibodies have different avidities that can be evaluated using modified enzyme-linked immunosorbent assay (ELISA) techniques. We determined levels and avidities of antibodies to light (NFL) and medium (NFM) subunits of neurofilaments and tau protein in serum and cerebrospinal fluid (CSF) from 26 patients and anti-tau antibody levels and their avidities in 20 multiple sclerosis (MS) patients and 20 age- and sex-matched controls. Each sample was analyzed using both standard ELISA and also using a similar ELISA protocol with the addition of urea. The avidities of anti-neurocytoskeletal antibodies were higher in the CSF than those in serum (anti-NFL, p < 0.0001; anti-tau, p < 0.01; anti-NFM, n.s.). There was no relationship between avidities in serum and CSF for individual anti-neurocytoskeletal antibodies. We did not observe the relationship among the avidities of various anti-neurocytoskeletal antibodies. The avidities of anti-tau antibodies in the CSF were significantly higher in the MS patients than those in the controls (p < 0.0001). The study demonstrates the differences in avidities of CSF or serum neurocytoskeletal antibodies measured as the urea resistance by ELISA method. Avidity determination of anti-neurocytoskeletal antibodies could contribute to the evaluation of the immunological status of patients.

Background: Antibodies against tau protein indicate an interaction between the immune system and the neurocytoskeleton and therefore may reflect axonal injury in multiple sclerosis (MS). Methodology/Principal Findings: The levels and avidities of anti-tau IgG antibodies were measured using ELISA in paired cerebrospinal fluid (CSF) and serum samples obtained from 49 MS patients and 47 controls. Anti-tau antibodies were significantly elevated intrathecally (p,0.0001) in the MS group. The CSF anti-tau antibody levels were lower in MS patients receiving therapy than those without treatment (p,0.05). The avidities of anti-tau antibodies were higher in the CSF than in the serum (MS group p,0.0001; controls p,0.005). Anti-tau avidities in the CSF were elevated in MS patients in comparison with controls (p,0.05), but not in serum. Conclusions: MS patients have higher levels of intrathecal anti-tau antibodies. Anti-tau antibodies have different avidities in different compartments with the highest values in the CSF of MS patients.

Objectives: To assess the relationship between maternal and umbilical serum concentrations of matrix metalloproteinases (MMP)-2,8,9, the soluble receptor for advanced glycation end products (sRAGE) and IL-10 0 and premature delivery and fetal inflammation. Methods: Maternal serum levels of MMPs, sRAGE, IL-10 and C-reactive protein (CRP) were determined in 67 women with preterm labor and in 38 healthy pregnant women of similar gestational age (GA). In the group with preterm labor we also determined umbilical concentrations of MMPs, IL-6 and sRAGE. The group with preterm labor was additionally divided based on the presence of funisitis and elevations of fetal umbilical IL-6 concentrations. Results: Maternal serum levels of MMP-2 and sRAGE were significantly lower in women with preterm labor compared to women with normal pregnancy. Additionally, within the group of women with preterm labor, maternal serum MMP-2 concentrations were significantly lower in the subgroup with funisitis and in the subgroup with elevated umbilical concentration of IL-6. Conclusion: Our results demonstrate significantly different serum concentrations of MMP-2 and sRAGE in women with preterm labor compared to healthy pregnant patients of the same GA.

Background and purpose: The aim of this study was to compare the levels of anti-tubulin antibodies (anti-TU) in cerebrospinal fluid (CSF) and serum using bovine tubulin as the antigen in one enzyme-linked immunosorbent assay (ELISA) method (anti-TUb antibodies) and a synthetic neuron-specific octapeptide of tubulin in a second ELISA method (anti-TUs antibodies). Methods: Paired CSF and serum samples were obtained from 34 multiple sclerosis (MS) patients, 13 patients with various other neurological diseases (control diseases) and 17 normal control patients (CN). Results: CSF levels of anti-TUs and anti-TUb antibodies were significantly lower in the CN group when compared to those in the MS group. On the contrary, serum levels of anti-TU antibodies did not differ among groups. The intrathecal synthesis of anti-TUs antibodies in comparison with anti-TUb was significantly increased in all groups. Significant correlations between anti-TUb and anti-TUs antibodies were observed in the CSF of all three groups. However, with regard to serum, a similar relationship was only found in the MS group. Conclusions: The estimation of anti-TU in CSF can contribute to the overall assessment of axonal damage; on the contrary serum anti-tubulin antibodies were not useful for differential purposes in MS. The antibodies to the neuron-specific portion of tubulin seemed to be synthesised predominantly intrathecally.