The Role of Age on Beta-Amyloid1–42 Plasma Levels in Healthy Subjects

Beta-amyloid (Ab) plaques have been observed in the brain of healthy elderlies with frequencies strongly influenced by age. The aim of the study is to evaluate the role of age and other biochemical and hematological parameters on Ab1–42 plasma levels in cognitively and neurologically normal individuals. Two-hundred and seventy-five normal subjects stratified by age groups (<35 years, 35–65 years, and >65 years) were included in the study. Ab1–42 plasma levels significantly correlated with age (rs = 0.27; p < 0.0001) in the whole sample, inversely correlated with age in the first age group (rs = 0.25, p = 0.01), positively correlated in the second group (rs = 0.22, p = 0.03), while there was no significant correlation in the older group (rs = 0.02, p = 0.86). Both age (b- estimate = 0.08; p < 0.001) and cholesterol (b-estimate = 0.03; p = 0.009) were significantly associated with Ab1–42 plasma level in multivariable analysis. However, only the association with age survived post hoc adjustment for multiple comparisons. The different effects of age on the Ab level across age groups should be explored in further studies to better understand the age-dependent variability. This could better define the value of plasma Ab as a biomarker of the Alzheimer neuropathology

Cerebrospinal fluid level of proNGF as potential diagnostic biomarker in patients with frontotemporal dementia

IntroductionFrontotemporal dementia (FTD) is an extremely heterogeneous and complex neurodegenerative disease, exhibiting different phenotypes, genetic backgrounds, and pathological states. Due to these characteristics, and to the fact that clinical symptoms overlap with those of other neurodegenerative diseases or psychiatric disorders, the diagnosis based only on the clinical evaluation is very difficult. The currently used biomarkers help in the clinical diagnosis, but are insufficient and do not cover all the clinical needs.MethodsBy the means of a new immunoassay, we have measured and analyzed the proNGF levels in 43 cerebrospinal fluids (CSF) from FTD patients, and compared the results to those obtained in CSF from 84 Alzheimer’s disease (AD), 15 subjective memory complaints (SMC) and 13 control subjects.ResultsA statistically significant difference between proNGF levels in FTD compared to AD, SMC and controls subjects was found. The statistical models reveal that proNGF determination increases the accuracy of FTD diagnosis, if added to the clinically validated CSF biomarkers.DiscussionThese results suggest that proNGF could be included in a panel of biomarkers to improve the FTD diagnosis

Predictors of Care Home Admission and Survival Rate in Patients With Syndromes Associated With Frontotemporal Lobar Degeneration in Europe

Background and Objectives Data on care home admission and survival rates of patients with syndromes associated with frontotemporal lobar degeneration (FTLD) are limited. However, their estimation is essential to plan trials and assess the efficacy of intervention. Population-based registers provide unique samples for this estimate. The aim of this study was to assess care home admission rate, survival rate, and their predictors in incident patients with FTLD-associated syndromes from the European FRONTIERS register-based study. Methods We conducted a prospective longitudinal multinational observational registry study, considering incident patients with FTLD-associated syndromes diagnosed between June 1, 2018, and May 31, 2019, and followed for up to 5 years till May 31, 2023. We enrolled patients fulfilling diagnosis of the behavioral variant frontotemporal dementia (bvFTD), primary progressive aphasia (PPA), progressive supranuclear palsy (PSP) or corticobasal syndrome (CBS), and FTD with motor neuron disease (FTD-MND). Kaplan-Meier analysis and Cox multivariable regression models were used to assess care home admission and survival rates. The survival probability score (SPS) was computed based on independent predictors of survivorship. Results A total of 266 incident patients with FTLD were included (mean age ± SD = 66.7 ± 9.0; female = 41.4%). The median care home admission rate was 97 months (95% CIs 86–98) from disease onset and 57 months (95% CIs 56–58) from diagnosis. The median survival was 90 months (95% CIs 77–97) from disease onset and 49 months (95% CIs 44–58) from diagnosis. Survival from diagnosis was shorter in FTD-MND (hazard ratio [HR] 4.59, 95% CIs 2.49–8.76, p &lt; 0.001) and PSP/CBS (HR 1.56, 95% CIs 1.01–2.42, p = 0.044) compared with bvFTD; no differences between PPA and bvFTD were found. The SPS proved high accuracy in predicting 1-year survival probability (area under the receiver operating characteristic curve = 0.789, 95% CIs 0.69–0.87), when defined by age, European area of residency, extrapyramidal symptoms, and MND at diagnosis. Discussion In FTLD-associated syndromes, survival rates differ according to clinical features and geography. The SPS was able to predict prognosis at individual patient level with an accuracy of;80% and may help to improve patient stratification in clinical trials. Future confirmatory studies considering different populations are needed.</p

Efecto de cultivos de cobertura de diferentes calidades sobre la materia orgánica de dos suelos venezolanos

La materia org&aacute;nica tiene gran influencia en las propiedades qu&iacute;micas, f&iacute;sicas y biol&oacute;gicas de los suelos, pero a su vez &eacute;sta es afectada tanto en cantidad como en calidad por las pr&aacute;cticas de manejo que se aplican al suelo. El objetivo de este estudio es comparar el efecto de diferentes cultivos de cobertura (gram&iacute;neas y leguminosas), utilizados como barbechos mejorados en un sistema de labranza conservacionista, sobre las diferentes fracciones de la MO, en dos suelos de caracter&iacute;sticas contrastantes. Para este estudio se seleccionaron un Vertisol arcilloso (San Pablo) y un Entisol arenoso (La Iguana), ambos en el estado Guarico (Venezuela), tomando muestras a tres profundidades y tres &eacute;pocas (a&ntilde;os 2000 y 2001). Se realiz&oacute; una caracterizaci&oacute;n inicial de ambos suelos y luego de la siembra del ma&iacute;z se evalu&oacute;: carbono org&aacute;nico total (COT), carbono extra&iacute;ble total&nbsp; (CET) fracci&oacute;n ligera (FL) y fracci&oacute;n pesada (FP) de&nbsp; la&nbsp; materia&nbsp; org&aacute;nica, &aacute;cidos&nbsp;h&uacute;micos (AH), &aacute;cidos f&uacute;lvicos (AF) y carbono en todas estas fracciones; tambi&eacute;n se calcularon los &iacute;ndices: C/N, grado de humificaci&oacute;n (DH), relaci&oacute;n de humificaci&oacute;n (HR), &iacute;ndice de humificaci&oacute;n (HI), CAH/CAF, CAF/COT. Los resultados indican diferencias entre ambos suelos, debido principalmente a su granulometr&iacute;a y a la calidad de las coberturas evaluadas, especialmente en el &iacute;ndice de humificaci&oacute;n.&nbsp;&nbsp;Palabras claves: Cultivos de cobertura, materia org&aacute;nica, Entisol, Vertisol.&nbsp;Abstract&nbsp;The different fractions of organic matter have a great influence on the chemical, physical and biological properties of the soils, and at the same time they are affected (in quantity and quality) by the management applied to them. Therefore, the objective of this study was to compare the effect of different cover crops (gramineous and leguminous) used as improved fallow for conservation tillage system on the organic matter fractions, in two contrasting soils. A clayey Vertisol (San Pablo) and sandy Entisol (La Iguana) were selected; both on Gu&aacute;rico state (Venezuela) and they were sampled at three depth and three moment for the development of the systems (years 2000 and 2001). It was evaluated: total organic carbon (TOC), total extracted carbon (TEC), light fraction content (LF) and heavy fraction conten (HF) of organic matter, humic acid (HA), fulvic acid (FA) and carbon in all fractions; also the index C/N, degree of humification (DH), humification rate (HR), humification index (HI), CHA/CFA, CFA/COT were calculated. The&nbsp; results&nbsp;&nbsp; indicated&nbsp;&nbsp; differences&nbsp; between&nbsp; both&nbsp;soils, due mainly to their granulometry and among the evaluated covers, especially in the humification index.&nbsp;Key words: Cover crops, organic matter, Vertisol, Entisol.&nbsp;&nbsp;&nbsp

Role of plasma phosphorylated neurofilament heavy chain (pNfH) in amyotrophic lateral sclerosis

The phosphorylated neurofilament heavy chain (pNfH) is a promising biomarker in amyotrophic lateral sclerosis (ALS). We examined plasma pNfH concentrations in order to corroborate its role as a diagnostic and prognostic biomarker in ALS. Incident ALS cases enrolled in a population- based registry were retrospectively selected and matched by sex and age with a cohort of healthy volunteers. Plasma pNfH levels were measured by an ELISA kit and correlated with clinical parameters. Discrimination ability of pNfH was tested using receiving operating characteristic (ROC) curves. Kaplan–Meier (KM) analysis and Cox proportional hazard models were used for sur-vival analysis. Plasma pNfH was significantly higher in patients compared to controls. An optimal cut-off of 39.74 pg/ml discriminated cases from controls with an elevated sensitivity and specificity. Bulbar-onset cases had higher plasma pNfH compared to spinal onset (p= 0.0033). Furthermore, plasma pNfH positively correlated with dis-ease progression rate (r= 0.19, p= 0.031). Baseline plasma pNfH did not influence survival in our cohort. Our findings confirmed the potential utility of plasma pNfH as a diagnostic biomarker in ALS. However, further studies with longitudinal data are needed to corroborate its prognostic value

Neuroimaging Findings in a Patient with Anti-IgLON5 Disease: Cerebrospinal Fluid Dynamics Abnormalities

Anti-IgLON5 disease is a recently described autoimmune neurodegenerative disorder characterized by insidious onset, slow progression and a variety of neurological features. Neuroimaging in most patients with anti-IgLON5 disease is normal or shows nonspecific findings. Here, we report a case of anti-IgLON5 disease presenting with parkinsonism, falls, sleep problems with severe nocturnal dyspnea attacks, dysphagia, and dysautonomia. Imaging findings were initially suggestive of progressive supranuclear palsy. An altered cerebrospinal fluid dynamic was found on an MRI as well as high-convexity hyperperfusion on a brain SPECT. Further case descriptions with neuroimaging are required to characterize cerebral and cerebrospinal fluid dynamics abnormalities in this rare condition

Data_Sheet_1_Cerebrospinal fluid level of proNGF as potential diagnostic biomarker in patients with frontotemporal dementia.docx

IntroductionFrontotemporal dementia (FTD) is an extremely heterogeneous and complex neurodegenerative disease, exhibiting different phenotypes, genetic backgrounds, and pathological states. Due to these characteristics, and to the fact that clinical symptoms overlap with those of other neurodegenerative diseases or psychiatric disorders, the diagnosis based only on the clinical evaluation is very difficult. The currently used biomarkers help in the clinical diagnosis, but are insufficient and do not cover all the clinical needs.MethodsBy the means of a new immunoassay, we have measured and analyzed the proNGF levels in 43 cerebrospinal fluids (CSF) from FTD patients, and compared the results to those obtained in CSF from 84 Alzheimer’s disease (AD), 15 subjective memory complaints (SMC) and 13 control subjects.ResultsA statistically significant difference between proNGF levels in FTD compared to AD, SMC and controls subjects was found. The statistical models reveal that proNGF determination increases the accuracy of FTD diagnosis, if added to the clinically validated CSF biomarkers.DiscussionThese results suggest that proNGF could be included in a panel of biomarkers to improve the FTD diagnosis.</p

Once-Daily Subcutaneous Irisin Administration Mitigates Depression- and Anxiety-like Behavior in Young Mice

Major depression is one of the most common psychiatric disorders worldwide, usually associated with anxiety. The multi-etiological nature of depression has increased the search for new antidepressant molecules, including irisin, for which, in a previous study, we tested its effect in young mice when administered intraperitoneally in a long-term intermittent manner. Here, we evaluated the effect of subcutaneous short-term irisin administration (100 µg/Kg/day/5 days) in male and female mice subjected to behavioral paradigms: Tail Suspension Test (TST), Forced Swim Test (FST), Elevated Plus Maze (EPM), and Y Maze (YM). Moreover, a qRT-PCR assay was performed to analyze the impact of irisin treatment on Pgc-1α/FNDC5 expression in the brain. A significant reduction in immobility time in TST and FST was observed in irisin-treated mice. Furthermore, irisin treatment significantly increased the number of entries and time spent in open arms, demonstrating its anxiolytic effect. Memory-enhancing effects were not reported in YM. Interestingly, no gender differences were observed in all behavioral tests. Overall, these results suggest that short-term subcutaneous irisin administration can exert an antidepressant and anxiolytic role, probably due to the activation of the Pgc-1α/FNDC5 system in the brain. Further investigation could lead to the identification of irisin as a new agent for the treatment of psychiatric disorders

Alteration of bacterial communities and organic matter in microbial fuel cells (MFCs) supplied with soil and organic fertilizer

International audienceThe alteration of the organic matter (OM) and the composition of bacterial community in microbial fuel cells (MFCs) supplied with soil (S) and a composted organic fertilizer (A) was examined at the beginning and at the end of 3 weeks of incubation under current-producing as well as no-current-producing conditions. Denaturing gradient gel electrophoresis revealed a significant alteration of the microbial community structure in MFCs generating electricity as compared with no-current-producing MFCs. The genetic diversity of cultivable bacterial communities was assessed by random amplified polymorphic DNA (RAPD) analysis of 106 bacterial isolates obtained by using both generic and elective media. Sequencing of the 16S rRNA genes of the more representative RAPD groups indicated that over 50.4% of the isolates from MFCs fed with S were Proteobacteria, 25.1% Firmicutes, and 24.5% Actinobacteria, whereas in MFCs supplied with A 100% of the dominant species belonged to gamma-Proteobacteria. The chemical analysis performed by fractioning the OM and using thermal analysis showed that the amount of total organic carbon contained in the soluble phase of the electrochemically active chambers significantly decreased as compared to the no-current-producing systems, whereas the OM of the solid phase became more humified and aromatic along with electricity generation, suggesting a significant stimulation of a humification process of the OM. These findings demonstrated that electroactive bacteria are commonly present in aerobic organic substrates such as soil or a fertilizer and that MFCs could represent a powerful tool for exploring the mineralization and humification processes of the soil OM