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Alzheimer’s disease (AD) is characterized by extracellular amyloid- β (A β ) deposition, which activates microglia, induces neuroinflammation and drives neurodegeneration. Recent evidence indicates that soluble pre-fibrillar A β species, rather than insoluble fibrils, are the most toxic forms of A β . Preventing soluble A β formation represents, therefore, a major goal in AD. We investigated whether microvesicles (MVs) released extracellularly by reactive microglia may contribute to AD degeneration. We found that production of myeloid MVs, likely of microglial origin, is strikingly high in AD patients and in subjects with mild cognitive impairment and that AD MVs are toxic for cultured neurons. The mechanism responsible for MV neurotoxicity was defined in vitro using MVs produced by primary microglia. We demonstrated that neurotoxicity of MVs results from (i) the capability of MV lipids to promote formation of soluble A β species from extracellular insoluble aggregates and (ii) from the presence of neurotoxic A β forms trafficked to MVs after A β internalization into microglia. MV neurotoxicity was neutralized by the A β -interacting protein PrP and anti-A β antibodies, which prevented binding to neurons of neurotoxic soluble A β species. This study identifies microglia-derived MVs as a novel mechanism by which microglia participate in AD degeneration, and suggest new therapeutic strategies for the treatment of the disease.

Frontotemporal Dementia (FTD) is a neurodegenerative disorder mainly characterised by Tau or TDP43 inclusions. A co-autoimmune aetiology has been hypothesised. In this study, we aimed at defining the pathogenetic role of anti-AMPA GluA3 antibodies in FTD. Serum and cerebrospinal fluid (CSF) anti-GluA3 antibody dosage was carried out and the effect of CSF with and without anti-GluA3 antibodies was tested in rat hippocampal neuronal primary cultures and in differentiated neurons from human induced pluripotent stem cells (hiPSCs). TDP43 and Tau expression in hiPSCs exposed to CSF was assayed. Forty-one out of 175 screened FTD sera were positive for the presence of anti-GluA3 antibodies (23.4%). FTD patients with anti-GluA3 antibodies more often presented presenile onset, behavioural variant FTD with bitemporal atrophy. Incubation of rat hippocampal neuronal primary cultures with CSF with anti-GluA3 antibodies led to a decrease of GluA3 subunit synaptic localization of the AMPA receptor (AMPAR) and loss of dendritic spines. These results were confirmed in differentiated neurons from hiPSCs, with a significant reduction of the GluA3 subunit in the postsynaptic fraction along with increased levels of neuronal Tau. In conclusion, autoimmune mechanism might represent a new potentially treatable target in FTD and might open new lights in the disease underpinnings.

In the last few years, an intense R &D activity on particle detectors for future HEP applications has been carried on with the aim of developing new techniques as well as studying the performance of already existing detectors when operated in a high rate environment. As for Resistive Plate Chamber detectors, the main challenges to face are the improvement of their detection capabilities and longevity at very high-rates, and the search for new eco-friendly gasmixtures free from greenhouse components. Results obtained in the framework of the RPC ECOGas@GIF++ Collaboration on a thin-Resistive Plate Chamber exposed at the CERN Gamma Irradiation Facility and operated with eco-friendly gas mixtures based on Tetrafluoropropene and Carbon dioxide will be discussed in this paper.

Publisher Erratum: Eur. Phys. J. C (2025) 85:737 https://doi.org/10.1140/epjc/s10052-025-14352-1 The author M. Pavan (affiliations 9 and 10) was missing from the published author list. The online version of the article has been updated to include the author. Additionally, affiliations 4 and 17 have been corrected to reflect the proper institutional order. The publisher apologizes for the inconvenience caused.

Results obtained by the RPC ECOgas@GIF++ Collaboration, using Resistive Plate Chambers operated with new, eco-friendly gas mixtures, based on tetrafluoropropene and carbon dioxide, are shown and discussed in this paper. Tests aimed to assess the performance of this kind of detectors in high-irradiation conditions, analogous to the ones foreseen for the coming years at the Large Hadron Collider experiments, were performed, and demonstrate a performance basically similar to the one obtained with the gas mixtures currently in use, based on tetrafluoroethane, which is being progressively phased out for its possible contribution to the greenhouse effect. Long term aging tests are also being carried out, with the goal to demonstrate the possibility of using these eco-friendly gas mixtures during the whole High Luminosity phase of the Large Hadron Collider.

Previous studies suggest that in Alzheimer's disease (AD) the Apolipoprotein E ( APOE) ε4 allele is associated with greater vulnerability of medial temporal lobe structures. However, less is known about its effect on the whole cortical mantle. Here we aimed to identify APOE-related patterns of cortical atrophy in AD using an advanced computational anatomy technique. We studied 15 AD patients carriers (ε4+, age: 72 ± 10 SD years, MMSE: 20 ± 3 SD) and 14 non-carriers (ε4−, age: 69 ± 9, MMSE: 20 ± 5) of the ε4 allele and compared them to 29 age-and-sex matched controls (age: 70 ± 9, MMSE: 28 ± 1). Each subject underwent a clinical evaluation, a neuropsychological battery, and high-resolution MRI. UCLA's cortical pattern matching technique was used to identify regions of local cortical atrophy. ε4+ and ε4− patients showed similar performance on neuropsychological tests ( p > .05, t-test). Diffuse cortical atrophy was detected for both ε4+ ( p = .0001, permutation test) and ε4− patients ( p = .0001, permutation test) relative to controls, and overall gray matter loss was about 15% in each patients group. Differences in gray matter loss between carriers and non-carriers mapped to the temporal cortex and right occipital pole (20% greater loss in carriers) and to the posterior cingulate, left orbitofrontal and dorsal fronto-parietal cortex (5–15% greater loss in non-carriers). APOE effect in AD was not significant ( p > .74, ANOVA), but a significant APOE by region (temporal vs fronto-parietal cortex) interaction was detected ( p = .002, ANOVA), in both early and late-onset patients ( p < .05, ANOVA). We conclude that the ε4 allele modulates disease phenotype in AD, being associated with a pattern of differential temporal and fronto-parietal vulnerability.

The INFN Cloud project was launched at the beginning of 2020, aiming to build a distributed Cloud infrastructure and provide advanced services for the INFN scientific communities. A Platform as a Service (PaaS) was created inside INFN Cloud that allows the experiments to develop and access resources as a Software as a Service (SaaS), and CYGNO is the betatester of this system. The aim of the CYGNO experiment is to realize a large gaseous Time Projection Chamber based on the optical readout of the photons produced in the avalanche multiplication of ionization electrons in a GEM stack. To this extent, CYGNO exploits the progress in commercial scientific Active Pixel Sensors based on Scientific CMOS for Dark Matter search and Solar Neutrino studies. CYGNO, like many other astroparticle experiments, requires a computing model to acquire, store, simulate and analyze data typically far from High Energy Physics (HEP) experiments. Indeed, astroparticle experiments are typically characterized by being less demanding of computing resources with respect to HEP ones but have to deal with unique and unrepeatable data, sometimes collected in extreme conditions, with extensive use of templates and montecarlo, and are often re-calibrated and reconstructed many times for a given data set. Moreover, the varieties and the scale of computing models and requirements are extremely large. In this scenario, the Cloud infrastructure with standardized and optimized services offered to the scientific community could be a useful solution able to match the requirements of many small/medium size experiments. In this work, we will present the CYGNO computing model based on the INFN cloud infrastructure where the experiment software, easily extendible to similar experiments to similar applications on other similar experiments, provides tools as a service to store, archive, analyze, and simulate data.

Since 2019, a collaboration between researchers from various institutes and experiments (i.e., ATLAS, CMS, ALICE, LHCb/SHiP and the CERN EP-DT group) has been operating several RPCs with diverse electronics, gas gap thicknesses and detector layouts at the CERN Gamma Irradiation Facility (GIF++). The studies aim at assessing the performance of RPCs when filled with new eco-friendly gas mixtures in avalanche mode and in view of evaluating possible aging effects after long high background irradiation periods, for example, high-luminosity LHC phase. This challenging research is also part of a task of the European AidaInnova project. A promising eco-friendly gas identified for RPC operation is the tetrafluoruropropene (C 3 H 2 F 4 , commercially known as HFO-1234ze) that has been studied at the CERN GIF++ in combination with different percentages of CO 2 . Between the end of 2021 and 2022, several beam tests have been carried out to establish the performance of RPCs operated with such mixtures before starting the irradiation campaign for the aging study. Results of these tests for different RPCs layouts and different gas mixtures, under increasing background rates are presented here, together with the preliminary outcome of the detector aging tests.

MOLECULAR PSYCHIATRY: (2002) 7, 136-139. DOI: 10.1038/sj.mp.4000952

CYGNO is a project realising a cubic meter demonstrator to study the scalability of the performance of the optical approach for the readout of large-volume, GEM-equipped TPC. This is part of the CYGNUS proto-collaboration which aims at constructing a network of underground observatories for directional Dark Matter search. The combined use of high-granularity sCMOS and fast sensors for reading out the light produced in GEM channels during the multiplication processes was shown to allow on one hand to reconstruct 3D direction of the tracks, offering accurate energy measurements and sensitivity to the source directionality and, on the other hand, a high particle identification capability very useful to distinguish nuclear recoils. Results of the performed R&D and future steps toward a 30-100 cubic meter experiment will be presented.