Introduction Amyloid, Tau, and neurodegeneration biomarkers can stage Alzheimer's Disease (AD). Synaptic biomarkers may help track cognition. Methods In cognitively normal controls, Mild Cognitive Impairment (MCI) and AD, we investigated CSF biomarkers in relation to cognitive measures and as predictors of cognitive and global decline. Results There were 90 normal controls (mean age 73.0, 58% women), 57 MCI (mean age 74.3, 35% women), and 46 AD (mean age 70.7, 41% women). CSF Aβ1‐42 and Neuronal Pentraxin 2 (NPTX2) were decreased, and CSF Tau, neurogranin, and SNAP25 increased in AD versus controls. Aβ1‐42/Tau or NPTX2/Tau discriminated AD and controls best. NPTX2/Tau correlated strongly with cognition in AD and MCI and predicted a 2–3‐year decline. We replicated findings in the ADNI cohort. Discussion CSF synaptic biomarkers, particularly NPTX2, which regulates synaptic homeostasis, relate to cognition and predict progression in AD beyond Aβ1‐42 and Tau. This is relevant for prognosis and clinical trials.

The soil fungus Trichoderma harzianum is a mycoparasitic fungus known for its use as a biocontrol agent of phytopathogenic fungi. Among other factors, Trichoderma produces a series of antibiotics and fungal cell wall-degrading enzymes. These enzymes are believed to play an important role in mycoparasitism. Among the hydrolytic enzymes, we have identified a basic proteinase (Prb1) which is induced by either autoclaved mycelia, fungal cell wall preparation or chitin; however, the induction does not occur in the presence of glucose. The proteinase was purified and biochemically characterized as a serine proteinase of 31 kDa and pI 9.2. Based on the sequence of three internal peptides, synthetic oligonucleotide probes were designed. These probes allowed subsequent isolation of a cDNA and its corresponding genomic clone. The deduced amino acid sequence indicates that the proteinase is synthesized as a pre-proenzyme and allows its classification as a serine proteinase. Northern analysis shows that the induction of this enzyme is due to an increase in the corresponding mRNA level.

This study strengthens the potential of neurogranin as an AD CSF biomarker, which now needs validation in larger studies. As tools, straightforward immunoassays can be used, as demonstrated by the described ELISA.

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C57BL/6, C3H, and BALB/c mice were vaccinated with plasmids encoding Toxoplasma gondii antigens GRA1, GRA7, and ROP2, previously described as strong inducers of immunity. Seroconversion for the relevant antigen was obtained in the majority of the animals. T. gondii lysate stimulated specific T-cell proliferation and secretion of gamma interferon (IFN-␥) in spleen cell cultures from vaccinated BALB/c and C3H mice but not in those from control mice. Although not proliferating, stimulated splenocytes from DNA-vaccinated C57BL/6 mice also produced IFN-␥. No interleukin-4 was detected in the supernatants of lysate-stimulated splenocytes from DNA-vaccinated mice in any of the mouse strains evaluated. As in infected animals, a high ratio of specific immunoglobulin G2a (IgG2a) to IgG1 antibodies was found in DNA-vaccinated C3H mice, suggesting that a Th1-type response had been induced. For BALB/c mice, the isotype ratio of the antibody response to DNA vaccination was less polarized. The protective potential of DNA vaccination was demonstrated in C3H mice. C3H mice vaccinated with plasmid encoding GRA1, GRA7, or ROP2 were partially protected against a lethal oral challenge with cysts of two different T. gondii strains: survival rates increased from 10% in controls to at least 70% after vaccination in one case and from 50% to at least 90% in the other. In vaccinated C3H mice challenged with a nonlethal T. gondii dose, the number of brain cysts was significantly lower than in controls. DNA vaccination did not protect BALB/c or C57BL/6 mice. Our results demonstrate for the first time in an animal model a partially protective effect of DNA vaccination against T. gondii.

BackgroundWhile neurogranin has no value as plasma biomarker for Alzheimer’s disease, it may be a potential blood biomarker for traumatic brain injury. This evokes the question whether there are changes in neurogranin levels in blood in other conditions of brain injury, such as acute ischemic stroke (AIS).MethodsWe therefore explored neurogranin in paired cerebrospinal fluid (CSF)/plasma samples of AIS patients (n = 50) from a well-described prospective study. In parallel, we investigated another neuronal protein, i.e. tau, which has already been suggested as potential AIS biomarker in CSF and blood. ELISA as well as Single Molecule Array (Simoa) technology were used for the biochemical analyses. Statistical analyses included Shapiro-Wilk testing, Mann-Whitney analyses and Pearson’s correlation analysis.ResultsIn contrast to tau, of which high levels in both CSF and plasma were related to stroke characteristics like severity and long-term outcome, plasma neurogranin levels were only correlated with infarct volume. Likewise, CSF neurogranin levels were significantly higher in patients with an infarct volume > 5 mL than in patients with smaller infarct volumes. Finally, neurogranin and tau were significantly correlated in CSF, whereas a weaker relationship was observed in plasma.ConclusionsThese findings indicate that although plasma and CSF neurogranin may reflect the volume of acute cerebral ischemia, this synaptic protein is less likely to be a potential AIS biomarker. Levels of tau correlated with severity and outcome of stroke in both plasma and CSF, in the present study as well as previous reports, confirming the potential of tau as an AIS biomarker.Electronic supplementary materialThe online version of this article (10.1186/s12883-017-0945-8) contains supplementary material, which is available to authorized users.

The hepatitis C virus (HCV) is the etiologic agent of non-A non-B hepatitis, the leading cause of chronic liver infections. Chronic HCV infection is correlated with the risk of developing liver cirrhosis and hepatocellular carcinoma (1). It is estimated that there are more than 170 million chronic carriers worldwide (44). To date, there is neither a prophylactic vaccine nor a satisfactory therapeutic treatment (27), and although routine testing of blood products for HCV has reduced posttransfusion infection in the Western world, not all of the routes of transmission are known, and new cases are still accumulating.The development of an HCV vaccine has been problematic due to the logistics and the ethical restrictions in the numbers and use of chimpanzees, the only species other than Homo sapiens that is susceptible to chronic HCV infection. Furthermore, essential information regarding the immune correlates of protective immunity is still lacking. Although important proof-of-principle ex vivo neutralization studies have been undertaken with chimpanzees (14), neutralizing antibodies are not easily attained and are considered insufficient for viral clearance or the prevention of reinfection (9, 13). The study of immune responses induced in individuals and chimpanzees with acute resolved versus chronic infections has so far revealed only an emerging picture of potential protective immune responses following the establishment of active viral infection. In addition to innate host immunity (38), the importance of cytotoxic T lymphocytes (CTLs) (9,12,18,43,46), gamma interferon (IFN-␥)-producing T cells homing into the liver (36), and T-helper (Th) responses (4,10,20,26) in the control of HCV infection has been demonstrated. However, the correlates of prophylactic vaccine protection following parenteral immunization are expected to be largely extrahepatic prior to HCV exposure. We set out to correlate such peripheral immune responses with vaccine efficacy in order to identify peripheral immune readouts that are likely to be indicative of a desirable vaccine-induced response. Such end points should be readily measurable in human volunteers without necessitating invasive liver biopsies.A limited number of vaccine efficacy studies have been performed with chimpanzees. Immunization with E1 and E2 proteins protected five out of seven animals from infection after a low-dose homologous challenge (with exactly the same clone being used for immunization and challenge) (8) but not against heterologous challenge. In another study, DNA expressing E2 was used to immunize two chimpanzees. Following homologous challenge, both vaccinees became infected but resolved the infection (15). However, none of these studies provided insights into the nature of the vaccine-induced immune correlates of clearance. In addition, HCV presents a high degree of variability (35). Multiple genotypes coexist worldwide, and in * Corresponding author. Mailing address: UMR 2142 CNRS/BioMerieux, 46 allee d'Italie,

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