Biosensor (Italy)

Cyclase-associated protein 2 (CAP2) is a synaptic actin-binding protein involved in cofilin-mediated spine remodelling, Alzheimer’s Disease synaptic failure and myofibril maintenance, indicating its potential involvement in motor neuron disease (MND). This study examined cerebrospinal fluid (CSF) levels of CAP2 in 60 patients with MND and 40 healthy controls (HC) to assess its diagnostic and prognostic value and its relationship with neuronal, glial and synaptic markers. Glial fibrillary acidic protein (GFAP), neurofilament light chain (NfL), phosphorylated and total tau (p-Tau 181, t-Tau), CAP2 and synaptosomal-associated protein 25 (SNAP-25) were quantified using ELISA, Lumipulse and SIMOA platforms. MND patients displayed increased GFAP, NfL, t-Tau, p-Tau 181 levels and CAP2 while SNAP-25 was reduced. CAP2 correlated with tau markers, but not with NfL or GFAP. Unlike NfL, which was higher in upper motor neuron–predominant cases and predicted faster progression and poorer survival, CAP2 did not vary with disease subtypes or severity. The study showed that CAP2 is associated with MND independently from neuronal, glial and presynaptic dysfunction. Integrating CAP2 into multi-marker panels could enhance understanding of synaptic pathology in MND.

Electrochemical reduction of graphene oxide (GO) is widely used to generate conductive reduced graphene oxide (rGO) films on microstructured electrodes, yet the evolution of electrical transport during the reduction process remains poorly understood. Here, we present a fully automated operando platform that enables time-resolved conductance monitoring during electrochemical GO reduction and correlates electrical transport with capacitive and structural changes. By integrating electrical two- and four-point measurements with impedance spectroscopy, we directly follow the emergence and in-plane expansion of electrochemically reduced GO domains. Raman spectroscopy identifies the reduction onset at approximately −0.6 V vs. Ag/AgCl, while operando measurements reveal potential-dependent growth kinetics and a strong correlation between conductance, capacitance, and film coalescence. Despite the intrinsic heterogeneity of drop-cast GO films, normalized conductance trajectories exhibit excellent reproducibility and reveal that the overpotential dictates the kinetic profile of rGO formation. The ability to directly resolve the emergence of rGO films and their formation kinetics provides a new level of process control for electrochemically fabricated rGO devices.

HighlightsWhat are the main findings?The first 2 min of the 6-min walk test (2’6MWT) correlate strongly with full 6MWT gait parameters, especially stride length and gait speed.Agreement between the 2’6MWT and full 6MWT remained consistent at 1- and 2-year follow-up, while the full test is needed to capture subtle fatigue-related changes.What is the implication of the main finding?The 2’6MWT can serve as a practical, time-efficient surrogate for gait assessment in patients with Parkinson’s disease.Using sensor-based gait analysis, clinicians and researchers can reliably monitor walking performance while reducing patient fatigue and clinical testing time, as both the 2-min and 6-min measures can be derived from a single walking session.Gait assessment is key in Parkinson’s disease (PD), but the psychometric properties of common tests like the 6-Minute Walk Test (6MWT) are not fully established. Inertial Measurement Units (IMUs) offer objective gait measures, potentially reducing repeated testing. This study evaluated whether the resampling of the first 2 min of the 6MWT (2’6MWT) reflects full-test performance in 43 early-to-mild PD patients (median age 65) at baseline, 1-year, and 2-year follow-ups. A trunk-mounted IMU recorded distance covered, walking duration, stride length, gait speed, cadence, and symmetry. Analysis focused on participants with complete longitudinal data from a multicenter original cohort of 62. Stride length and gait speed (2’6MWT vs. 6MWT) demonstrated strong correlations (r > 0.98), near-perfect agreement, <5% error, and stability across follow-ups; cadence showed slightly more variability. The analysis of consecutive 2-min intervals of the 6MWT revealed stable stride length and gait speed, with modest decreases in distance and cadence over time. Exploratory associations of 2’6MWT and 6MWT with motor severity and cognitive status were consistent. These results indicate the 2’6MWT is a reliable, time-efficient alternative to the full 6MWT for assessing walking capacity in PD, especially in outpatient or fatigue-prone patients. The full 6MWT remains valuable for detecting subtle endurance- or fatigue-related changes.

DNA Origami In article number 2502496, Tania Patiño Padial and co-workers highlights real-time single-particle tracking of ligand-functionalized DNA origami nanorods interacting with cell membranes. Leveraging the spatial programmability of DNA origami, this approach enables precise interrogation of receptor-ligand binding kinetics and dynamics at the cell surface, offering new insights into nanoscale biointerfaces with high spatial and temporal resolution.

Neuropsychiatric symptoms, such as apathy, disinhibition and irritability, are common in Progressive Supranuclear Palsy (PSP). The Frontal Behaviour Inventory (FBI) is a useful instrument for the evaluation of behavioural disorders in neurodegenerative diseases. The main goal of the present study was to explore the psychometric properties of the FBI in PSP. FBI was administered to the PSP-NET cohort including Italian patients diagnosed according to the Movement Disorder Society criteria. Patients underwent a clinical interview, a motor evaluation, extensive cognitive and behavioural testing. Two hundred and eight subjects were included in this study. The internal consistency was high (Cronbach's alpha = 0.868) and no improvement of this value was noted upon removal of any item. FBI showed also good acceptability, reliability and validity. The standard error of measurement (SEM) value for FBI total score was 0.169 [SEM = SD √ (1 - Cronbach's alpha)]. Factor analysis indicated a five-factor structure: Apathy, Behavioural disorders, Impulsivity, Motor and speech frontal behaviour and Executive disorders that explained the 54.92% of the total variance. Linear regression analysis showed that global cognitive impairment significantly affects both Apathy and Motor and speech frontal behaviour factors. In conclusion, FBI is a reliable and valid tool for the assessment of neuropsychiatric symptoms in PSP, despite some constructs, such as euphoria and irritability, are better measured by the NPI. Two third of the cohort was represented by Richardson's syndrome, thus our data are mainly applicable to such common phenotype. Such data are useful in both clinical and research settings to plan adequate therapeutic interventions and to improve the quality of life of PSP patients and their caregivers.

The recent development of new methods to detect misfolded α-synuclein (αSyn) aggregates in biofluids and tissue biopsies in the earliest Parkinson’s disease (PD) phases is dramatically challenging the biological definition of PD. The αSyn seed amplification methods in cerebrospinal fluid (CSF) showed high sensitivity and specificity for early diagnosis of PD and Lewy bodies disorders. Several studies in isolated REM sleep behavior disorders and other at-risk populations also demonstrated a high prevalence of CSF αSyn positivity and its potential value in predicting the phenoconversion to clinically manifested diseases. Growing evidence exists for αSyn aggregates in olfactory mucosa, skin, and other tissues in subjects with PD or at-risk subjects. DOPA decarboxylase and numerous other candidates have been additionally proposed for either diagnostic or prognostic purposes in earliest PD phases. The newly described αSyn detection in blood, through its quantification in neuronally-derived exosome vesicles, represents a technical challenge that could open a new scenario for the biological diagnosis of PD. Despite this growing evidence in the field, most of method of αSyn detection and markers still need to be validated in ongoing longitudinal studies through an accurate assessment of different prodromal disease subtypes and scenarios before being definitively implemented in clinical settings.

Melatonin is a clinically important hormone as it plays a key role in maintaining immune system, circadian rhythm, blood pressure and cortisol levels. Therefore, its real time detection is crucial for monitoring body function. Melatonin detection by electrochemical sensors exhibits advantages such as high sensitivity, point-of-care analysis, rapid response time, easy to use and cost-effective. Natural polymer based biocomposites including chitosan, gum acacia, xanthan gum, chitin are widely employed due to their ready availability, low cost, biocompatibility and high surface area for biosensing applications. Herein, we investigated tungsten oxide (WO3) nanospheres decorated with functionalized chitosan (FCH) for melatonin detection. The functionalization of chitosan introduced plentiful amine groups and inter-hydrogen bonding that are essential for the formation of WO3/FCH biocomposite. Further, the large density of amine groups offered efficient binding affinity with WO3 and improved the conductivity of the nanocomposite thereby enabling sensitive melatonin detection. Electroanalysis confirmed the excellent electrocatalytic performance of the biocomposite towards melatonin with a limit of detection of 4.9 nM. The proposed nanocomposite exhibited excellent selectivity, reproducibility, stability. Further, its practical reliability was evaluated in real samples thereby demonstrating its usefulness in the detection of clinically relevant biomolecules.

Extracellular calcium ion ([Ca2+]o) change occurring during physiological and pathological conditions play important roles in regulation of brain functions, but has received limited attention due to the lack of easy to use device. Here, we show the development and application of highly selective calcium image sensor for the imaging of glutamate-induced [Ca2+]o change in hippocampal slices. Using this sensor, we found that glutamate decreased [Ca2+]o by more than 50 % with different spatiotemporal patterns. The glutamate-evoked decrease in [Ca2+]o was inhibited by a NMDA receptor antagonist D-AP5 but not AMPA receptor antagonist CNQX, and mimicked by NMDA. The spatial pattern of the glutamate-evoked [Ca2+]o decrease was associated with that of distribution of NMDA receptors in the hippocampus. Moreover, using an ATP-imaging fluorescent probe, we found that the stimulation with NMDA triggered increase in ATP release from astrocytes via either connexin hemichannels or chloride channels. The NMDA-evoked ATP release was mediated by decrease in [Ca2+]o because the astrocytic ATP release was mimicked by Ca2+-free medium. Taken together, using the newly developed Ca2+ image sensor, we demonstrated that [Ca2+]o is dramatically decreased during excitatory synaptic transmission by glutamate, and [Ca2+]o decrease act as a signal that transmits neuronal excitation to astrocytes via ATP release. The application of this Ca2+ sensor is expected to clarify the physiological and pathophysiological roles of [Ca2+]o , which have received limited attention so far.