Search Results (8,599)

Alzheimer’s disease (AD) has been conceptualised as a proteinopathy driven by amyloid-β plaques and hyperphosphorylated tau neurofibrillary tangles. AD should not be understood as exclusively a proteinopathy or a metabolic/redox disorder, but as a network of interacting processes in which metabolic dysfunction, mitochondrial impairment, redox dysregulation, amyloid-β, tau, neuroinflammation, metal dyshomeostasis, and regulated cell death reinforce one another. This review examines AD through a redox-metabolic framework integrating cerebral glucose metabolism, insulin signalling, mitochondrial bioenergetics, metal homeostasis, and regulated cell death. We discuss how glucose hypometabolism, impaired oxidative phosphorylation, and weakened antioxidant defences may promote reactive oxygen species production and self-reinforcing oxidative and metabolic dysfunction. We examine interactions with amyloid-β and tau pathology, glial immunometabolism, gut–brain signalling, neuroinflammation, and metal-mediated toxicity. Advances in multi-omics, blood-based metabolomic and lipidomic biomarkers, and imaging may enable earlier biological stratification. Therapeutic strategies targeting mitochondria, NRF2 signalling, metabolic dysfunction, metal dyshomeostasis, and regulated oxidative cell death are evaluated based on current evidence and their potential complementarity with amyloid-directed therapies. Although temporal relationships remain unresolved, redox-metabolic dysfunction may represent an early determinant and amplifier of neuronal vulnerability. Evidence for lecanemab and donanemab supports an integrative rather than replacement model of AD treatment. This framework may facilitate earlier diagnosis, patient stratification, and complementary disease-modifying interventions. Full article

Background: The ingestion of polyunsaturated fatty acids is vital for brain health, supporting cognitive development and helping to prevent chronic diseases, including neurodegenerative processes. Objective: This study aimed to investigate the effects of corn oil on the biochemical and neurochemical parameters of Drosophila melanogaster expressing human amyloid precursor protein β42 (APP-β₄₂). Methods: The flies were fed a diet supplemented with 37.8 mg/mL of corn oil from the larval stage until adulthood. Results: A diet supplemented with corn oil induced significant changes in biochemical markers, such as a decrease in head cholesterol levels (p < 0.001); decreased catalase activity and hydrogen peroxide levels in the heads (p < 0.0001) and thoracic muscles (p < 0.0001); reduced glutathione levels in the heads (p < 0.0001) and muscles (p < 0.01); and reduced formazan production (p < 0.01) and citrate synthase (CS) activity (p < 0.0001) in the head. However, in thoracic muscle, ingestion of corn oil led to an increase in formazan production (p < 0.01) and no significant change in CS activity. Lactate levels decreased in the heads (p < 0.0001) and thoraces (p < 0.001) after flies were fed corn oil. Finally, ingestion of corn oil resulted in a significant rise in acetylcholinesterase activity in the heads (p < 0.001) and thoracic muscles (p < 0.01). Conclusions: These results suggest that consuming corn oil reduces the oxidative stress typical of an Alzheimer’s disease model by enhancing antioxidant defenses. Full article

Background/Objectives: Quantitative magnetic resonance imaging (MRI) volumetry may provide an objective approach for detecting subtle longitudinal structural brain changes in patients with epilepsy. This retrospective longitudinal study investigated regional and global brain volume changes observed during levetiracetam (LEV) monotherapy. Methods: Thirty-seven adults with epilepsy who underwent brain MRI before initiation of LEV monotherapy (MRI-1) and approximately 12 months later (MRI-2) were included. Automated volumetric segmentation was performed using volBrain, and within-subject changes in macrostructural, subcortical, and cortical volumes were evaluated. Results: No significant longitudinal changes were detected in global macrostructural measures, including white matter, gray matter, cerebrospinal fluid, total intracranial cavity, cerebral, cerebellar, brainstem, or ventricular volumes (all p > 0.05). In contrast, significant volume reductions were observed in the bilateral putamen, caudate nuclei, and thalami, as well as the left nucleus accumbens, bilateral insular cortex, and left occipital cortex (p < 0.05), whereas the right globus pallidus volume increased significantly. Conclusions: These findings demonstrate region-specific longitudinal volumetric changes during LEV monotherapy despite preserved global brain volumes. However, because this study lacked a longitudinal healthy control group, the observed changes cannot be definitively attributed to LEV and may also reflect epilepsy-related processes, normal aging, or other clinical factors. Automated MRI volumetry may represent a promising quantitative approach for longitudinal assessment, but its potential biomarker utility requires validation in larger prospective studies incorporating protocol-harmonized healthy controls and detailed clinical and treatment-exposure measures. Full article

Glycosaminoglycans (GAGs) are structurally diverse polysaccharides that regulate inflammation, coagulation, and cellular homeostasis through highly specific sulfation patterns and interactions with cationic proteins. Among GAG derivatives, 2-O, 3-O desulfated heparin (ODSH) is a chemically modified heparin derivative characterized by markedly reduced anticoagulant activity yet preserved affinity for key inflammatory mediators. This review summarizes current knowledge on ODSH structure–function relationships, molecular mechanisms, and therapeutic applications across inflammatory, vascular, and immune-mediated diseases. ODSH modulates several convergent pathogenic processes, including HMGB1-RAGE/TLR4 signaling, neutrophil elastase-mediated tissue injury, PF4-dependent platelet activation, selectin-mediated adhesion, and thrombin-induced endothelial permeability. These actions arise from both direct molecular interactions and indirect sequestration of extracellular mediators, collectively associated with reduced cytokine release, enhanced endothelial barrier stability, and attenuation of inflammation–coagulation crosstalk. Preclinical studies report protective effects in acute lung injury, cystic fibrosis, ischemia–reperfusion injury, traumatic brain injury, thrombocytopenia, and metastatic cancer. Some pilot clinical observations in acute myeloid leukemia and septic peritonitis have reported favorable biological effects. Despite multimodal activity, limitations include incomplete pharmacokinetic characterization, limited comparative studies with other desulfated heparins, and the need for dose–response and safety evaluation in human trials. Overall, available evidence suggests that ODSH may have therapeutic relevance in diseases characterized by excessive inflammation, endothelial dysfunction, and dysregulated host responses. This review integrates current evidence to guide future mechanistic and translational investigation into ODSH and related low-anticoagulant heparin derivatives. Full article

Understanding neuroimmune responses during brain infections remains challenging because the site of disease (i.e., the brain) is difficult to access, immune responses within the central nervous system (CNS) are spatially and temporally compartmentalized, and peripheral immune cells have largely served as a proxy for the neuroimmune response. Cerebrospinal fluid (CSF) occupies a unique anatomical and immunological position at the interface between the brain parenchyma, CNS border compartments, and the peripheral immune system, making it an important window through which neuroinflammatory processes can be investigated in living patients. In this review, we examine evidence from CNS infections, with particular emphasis on tuberculous meningitis, demonstrating that CSF contains cellular and transcriptional profiles that differ from those observed in peripheral blood and vary according to the anatomical sampling site. We consider how CNS-resident cells, border-associated immune populations, and recruited leukocytes contribute to the neuroimmune environment of CSF. Importantly, we distinguish evidence derived from cells directly recovered from CSF from soluble biomarkers that may reflect activity in parenchymal or border compartments, and from cellular processes inferred from transcriptomic studies. We also discuss how CSF sampling and analytical approaches influence interpretation and highlight the potential of high-dimensional profiling to resolve compartmentalized neuroimmune responses during CNS infection. Full article

Visual working memory (vWM) undergoes age-related decline, affecting storage capacity, representational precision, feature binding, and inhibitory control, with consequences for everyday functioning. Nevertheless, accumulating evidence indicates that the aging brain retains substantial plasticity, providing an opportunity of intervention. This review synthesizes current evidence on approaches to improving vWM in healthy older adults, including classic and game-based cognitive training, non-invasive brain stimulation (NIBS), and multimodal protocols that combine cognitive training with physical exercise or brain stimulation. Across the literature, process-based cognitive training produces improvements on trained and closely related tasks, whereas evidence for durable far-transfer remains limited. NIBS demonstrates promising neurophysiological effects, particularly when targeting frontoparietal networks, although behavioral outcomes remain heterogeneous and appear to depend on stimulation parameters and individual characteristics. Emerging findings further suggest that combining interventions may enhance selected aspects of vWM, highlighting the importance of personalized approaches. Despite these advances, intervention effects are often modest, task-specific, and resource-intensive. As a complementary approach, the review proposes placebo and nocebo effects as a theoretically grounded hypothesis that warrants empirical investigation for potentially complementing existing interventions and promoting healthy cognitive aging rather than confounds. Full article

Obesity–depression comorbidity involves interconnected metabolic dysfunction, chronic low-grade inflammation, oxidative stress, neuroendocrine dysregulation, gut microbial dysbiosis, and impaired gut–brain communication. Edible and medicinal mushrooms provide nutrients and diverse bioactive compounds, including polysaccharides, terpenoids, nucleosides, sterols, peptides, and phenolic compounds. This narrative review integrates evidence on representative mushroom species, cultivation and fermentation factors affecting their composition, major bioactive compounds and biosynthetic pathways, gut–brain axis-related mechanisms, and opportunities for functional food development. Evidence derived predominantly from in vitro and animal studies suggests that mushroom-derived bioactive compounds may modulate gut microbial composition, intestinal barrier integrity, inflammatory and oxidative pathways, lipid and glucose metabolism, and neuroendocrine signaling. An exploratory database-based analysis further mapped predicted candidate molecular targets associated with inflammatory, metabolic, and neural processes. From a food science perspective, the compositional diversity of mushrooms and their compatibility with cultivation, fermentation, extraction, and formulation provide opportunities for developing conventional foods, functional foods, nutraceuticals, and standardized products. Overall, edible and medicinal mushrooms show promise as food and nutraceutical resources, but their translation into evidence-based functional products requires improved standardization, safety and bioavailability assessments, and well-designed human trials. Full article

Alzheimer’s disease (AD) is now widely accepted as a complex disorder involving multiple interconnected pathological processes. Increasing evidence suggest that neuroinflammation and immune system dysregulation actively contribute to neurodegeneration, extending beyond the traditional view that the disease is driven solely by amyloid-β (Aβ) and tau pathology. With the advent of studies showing anti-amyloid antibodies to have only modest effects with significant toxicity, there has been a growing interest in investigating non-amyloid non-tau (NANT) treatment approaches. This review provided a general review of small molecules for neuroinflammation-based NANT therapies in AD. We reviewed several agents that affect the brain/immune axis, namely, kinase inhibitors (nelflamaimod and masitinib), NLRP3 inflammasome inhibitors (MCC950, selnoflast, and dapansutrile), TREM2 activators (VG-3927), gingipain inhibitors, PPARγ activators, KCa3.1 inhibitors, and repurposed drugs such as ambroxol and cromolyn. Some common drawbacks were identified for the drugs that failed to provide their anticipated effects. It was found that they all suffered from late-stage treatment, patient heterogeneity, inadequate central nervous system penetration, and poorly designed preclinical studies. Additional translational challenges included sex-specific differences in neuroimmune responses, APOE ε4-associated immune dysfunction, and the need for biomarker-guided patient selection. Although immune-targeted therapies remain strongly supported by biological evidence in AD, meaningful clinical progress will likely require earlier intervention strategies guided by biomarkers and therapies capable of targeting multiple disease pathways simultaneously. Full article

Exercise is a pivotal non-pharmacological intervention for enhancing overall health, with a key underlying mechanism being the induction of adaptive angiogenesis across multiple organ systems. This narrative review discusses recent advances in exercise-induced angiogenesis, with a particular focus on its tissue- and organ-specific manifestations and underlying molecular mechanisms. The available evidence indicates that exercise integrates diverse signals—including mechanical stress, metabolic shifts, and hypoxic or ischemic stress—to upregulate key angiogenic factors, such as vascular endothelial growth factor (VEGF), angiopoietin-1 (Ang-1) and angiopoietin-2 (Ang-2), and to activate conserved signaling pathways including hypoxia-inducible factor-1α (HIF-1α), phosphoinositide 3-kinase/protein kinase B (PI3K/Akt), and endothelial nitric oxide synthase (eNOS), thereby driving angiogenesis. This process exhibits tissue specificity: in skeletal muscle, it primarily enhances oxygen transport and metabolic efficiency; in bone, it couples with osteogenesis to maintain structural integrity; in the brain, it supports neuroplasticity and cognitive function; in the heart, it improves myocardial perfusion via angiogenesis and collateral remodeling (arteriogenesis); and in adipose tissue, it ameliorates the metabolic microenvironment. Furthermore, the mode and intensity of exercise, along with individual differences (such as age and health status), significantly influence the magnitude of its angiogenic effects. Accordingly, this review highlights the proposed role of exercise-induced angiogenesis in a range of conditions—including cardiovascular disease, sarcopenia, osteoporosis, neurodegenerative disorders, and metabolic syndrome—and we treat these relationships as potential mechanisms that require further validation rather than established therapeutic pathways. In the future, research should aim to define optimal exercise parameters, elucidate deeper molecular mechanisms, and investigate the translational potential of these insights for personalized clinical interventions. Full article

Viral infections have been associated with multiple sclerosis (MS), Alzheimer’s disease (AD), Parkinson’s disease (PD), and amyotrophic lateral sclerosis (ALS), but the associations may reflect different relationships to the disease process. This review evaluates evidence for viral involvement in disease initiation, modification of established disease, impaired viral control secondary to disease or treatment, and incidental detection. The strongest temporal evidence concerns Epstein–Barr virus (EBV) and MS. Prospective data place EBV seroconversion before clinical onset and the first observed increase in serum neurofilament light chain, while mechanistic studies link EBV infection, B-cell biology, and CNS-directed immunity. However, evidence that ongoing EBV activity modifies established MS remains limited. In AD, experimental studies support interactions between herpesviruses and AD-associated proteins, while the reduced incidence of all-cause dementia after herpes zoster vaccination suggests that viral or immunological pathways may be modifiable, without establishing that a specific herpesvirus initiates AD. Viral associations in PD rely mainly on epidemiological, experimental, and postmortem findings. Human pegivirus detection in a subset of PD brains remains a candidate association requiring independent confirmation and evidence of biological activity. Evidence in ALS is similarly limited. Enterovirus detection has been inconsistent, and altered human endogenous retrovirus K (HERV-K) expression in postmortem tissue does not establish an acquired viral infection. Stronger inference across these diseases will require longitudinal studies relating viral activity and antiviral immunity to subsequent disease-related changes, together with intervention studies that document the intended effect on the implicated viral process and separately assess subsequent disease risk or progression. Full article

Reducing user-specific calibration is critical for practical steady-state visual evoked potential (SSVEP)-based brain–computer interfaces (BCIs), yet few-shot cross-subject decoding remains challenged by heterogeneous source transferability and inter-subject variability. We propose SQ-HAF, a source quality-guided framework that combines target-relevant source selection, frequency neighborhood-regularized spatial filtering, covariance alignment, and multi-branch decision fusion. Candidate source subjects are ranked primarily by target–source template similarity; when more than one labeled calibration trial per stimulus is available, split-half template consistency (STC) provides a bounded confidence adjustment. The retained source data are used to construct aligned generalized and source-specific templates. For recognition, SQ-HAF fuses a five-subband harmonic reference CCA score with generalized source template and source-specific template scores. We evaluated SQ-HAF using leave-one-subject-out validation on the 35-subject Benchmark and 70-subject BETA datasets. Under the 1.0 s protocol with one labeled calibration trial per stimulus, the complete SQ-HAF configuration achieved 81.57% accuracy (ACC) and 227.83 bits/min information transfer rate (ITR) on Benchmark, and 65.56% ACC and 163.42 bits/min ITR on BETA. In a matched 0.5 s analysis with two calibration trials per stimulus, the five-subband harmonic reference design improved ACC over single-band processing on both datasets after Holm correction. These results indicate that target-relevant source screening and complementary harmonic/template evidence can support low-calibration cross-subject SSVEP decoding. Full article

Sparse Tucker decomposition (STD) is a framework for tensor decomposition that extends the classical Tucker model with sparsity constraints, with the aim of achieving better representation and analysis of multidimensional data. STD has attracted growing interest from various scientific fields, such as neuroimaging, machine learning, telecommunications, statistical computing, and brain connectivity analysis, due to its flexibility and computational efficiency. The purpose of this study is to present a systematic and structured review of the scientific literature on STD, describing its main trends, applications, and the evolution of research over time. Methods: A systematic review was conducted in accordance with the PRISMA 2020 guidelines using the Scopus and Web of Science databases. The search retrieved 21 records, of which 13 were selected for detailed analysis according to the established inclusion criteria. To improve the evaluation process, the selected studies were assessed using the plithogenic neutrosophic hypersoft set framework, which allowed for the evaluation of scientific contributions in terms of degrees of truth, indeterminacy, and falsity. The evaluation covered aspects such as methodological rigor, citation impact, thematic relevance, journal quality, and international collaboration networks. Results: Research on STD spans 2013 to 2025—the year of the first indexed record through the search date—and shows a marked increase after 2021. Five main application domains were identified: computational optimization, neuroimaging and neuropsychology, telecommunications, statistical analysis, and studies on brain connectivity. The literature on STD is still relatively limited and geographically concentrated, especially in the United States and China, despite the strong interdisciplinary potential and the growing scientific relevance of STD. Conclusions: STD is symmetric by construction, treating every tensor mode and component equally and applying the same sparsity penalty throughout, yet the literature surrounding it is markedly uneven, being concentrated in a few countries and a small number of technical fields. The PNHS framework allowed us to characterize this mismatch while accounting for the uncertainty of each judgement, scoring productivity, impact, collaboration, and thematic relevance through separate degrees of truth, indeterminacy, and falsity. This study identifies STD as a promising interdisciplinary analytical framework and demonstrates the value of plithogenic neutrosophic hypersoft methodologies for evaluating the scientific literature under uncertainty and multidimensionality. The review emphasizes the need for greater methodological standardization, increased international collaboration, and more robust interdisciplinary dissemination to establish STD as a robust framework for the analysis of multidimensional data. Full article

Epilepsy affects approximately 50 million people worldwide, and timely, accurate seizure detection is essential for clinical management. Electroencephalogram (EEG) signals carry rich temporal and spectral information about brain dynamics, yet manual interpretation is time-consuming and expert-dependent. This paper presents a complete automated EEG classification pipeline combining signal processing feature engineering with supervised machine learning to distinguish epileptic from non-epileptic brain states. Using the UCI Epileptic Seizure Recognition Dataset (11,500 segments of approximately 1.025 s and five classes at 173.61 Hz), we extract 31 features spanning the time domain (mean, standard deviation, RMS, peak-to-peak, zero-crossing rate, skewness, kurtosis, Hjorth activity, mobility, complexity, line length, mean absolute deviation, and derivative variance) and the frequency domain (DFT magnitude statistics and Welch PSD statistics, spectral entropy, spectral centroid, spectral bandwidth, total power, EEG band powers (delta through gamma), and inter-band power ratios). Four classifiers—logistic regression (LR), random forest (RF), support vector machine (SVM), and gradient boosting (GB)—are trained and evaluated on a binary task (seizure versus non-seizure) and a five-class task. For binary classification, the SVM achieves the highest accuracy of 99.13% with an F1 score of 0.978. For multiclass classification, gradient boosting achieves 81.35% accuracy. Feature importance analysis identifies the Hjorth complexity, spectral centroid, and theta-band power as the most discriminative features. A comprehensive ablation study further confirms that the combined 31-feature representation outperforms either domain in isolation by up to 4.2 percentage points on the multiclass task. Unlike less interpretable deep learning models, the proposed signal processing pipeline is computationally efficient and provides transparent feature-based classification on this benchmark dataset. The complete pipeline is implemented in Python 3.13.15 and is fully reproducible. Full article

Obesity is recognized as a pathological condition that induces chronic low-grade systemic inflammation capable of affecting multiple organs, including the central nervous system, thereby promoting neuroinflammation. Although adipose and neural tissues differ in their structural and functional characteristics, they share common inflammatory mechanisms involving the TLR4/NF-κB/MAPK signaling pathways, the ROS/NRF2 axis, and the NLRP3 inflammasome. This review summarizes current evidence demonstrating the ability of berberine (BBR) to modulate these shared molecular pathways across different experimental models and pathophysiological conditions, with particular emphasis on obesity-induced neuroinflammation. A narrative literature search was conducted using academic search and indexing resources, including PubMed, Scopus, Web of Science, and Google Scholar, with the literature updated through 24 August 2026. The available evidence indicates that BBR modulates these signaling pathways, reduces the production of pro-inflammatory cytokines, attenuates oxidative stress, and limits glial activation. Furthermore, several studies suggest that BBR may help preserve the functional integrity of the blood–brain barrier and reduce neuronal damage associated with neuroinflammatory processes. Available evidence suggests that BBR may modulate inflammatory and oxidative pathways involved in obesity-associated neuroinflammation; however, current findings derive mainly from preclinical studies and indirect models. Future studies are needed to determine the bioavailability, central nervous system penetration, and clinical relevance of BBR. Full article

Alzheimer’s disease (AD) is associated with both mild and moderate to severe traumatic brain injury (TBI). This narrative review gives an account of the association of TBI and AD and highlights possible cellular and molecular pathways linking these pathologies. Following TBI, the immune system of the brain is rapidly activated and gives rise to acute neuroinflammation. While neuroinflammation is protective in nature, it may persist chronically in the case of less-controlled prolonged responses, triggering neuroprotective loss and neurotoxicity. Moreover, reduced clearance of amyloid-beta may occur, along with its overproduction and aggregation. Tau protein regulation is also altered by kinase and phosphatase enzymes, resulting in the accumulation of hyperphosphorylated tau protein in neurons and glial cells and the emergence of intracellular tau neurofibrillary tangles. More to the point, vascular impairment following TBI has been reported to contribute to cognitive decline and AD. Blood–brain barrier breakdown following TBI allows for infiltration of peripheral immune cells and blood-derived proteins into the brain, which exacerbates neuroinflammation, interrupts synaptic signaling, and promotes oxidative stress. The neuroinflammatory response, dynamic alterations in amyloid and tau biology, and vascular impairment are thought to interact within a broader network of processes associated with AD neurodegeneration, rather than acting as isolated mechanisms. Full article