Search Results (582)

Early diagnosis of Alzheimer’s disease (AD) can facilitate the establishment and implementation of therapeutic interventions. The currently used diagnosis methods for AD mainly include cerebrospinal fluid analysis and positron emission tomography imaging. Due to their high invasiveness, high cost, and limited accessibility, these technologies are difficult to meet the needs of large-scale population screening, grading diagnosis, and treatment, thereby limiting the popularization of early diagnosis of AD. The detection of blood biomarkers has become an important breakthrough in early screening and diagnosis of different diseases due to its non-invasive, low-cost, and easy-to-operation advantages. Recently, blood proteins such as amyloid-beta (Aβ), total and phosphorylated Tau, light chain neurofilaments (NFL), and glial fibrillary acidic protein (GFAP) have been considered promising biomarkers for the diagnosis of AD. However, there is currently no effective, minimally invasive, and easily accessible detection method for clinical diagnosis and risk prediction of AD. Electrochemical and electrical biosensors are highly sensitive, simple, fast, and cost-effective analytical tools for disease monitoring, drug development, and target detection. In this work, we comprehensively and systematically overview the progress of various electrochemical and electrical techniques for determining AD-related blood protein biomarkers, mainly including electrochemistry, electrochemiluminescence, photoelectrochemistry, quartz crystal microbalance, field-effect transistor, and organic electrochemical transistor. This work can provide guidance for researchers to develop novel electrochemical and electrical biosensors for early and accurate diagnosis of AD. Full article

Parkinson’s disease (PD) is the second most common age-related neurodegenerative disorder, yet it remains unclear whether cortical architecture can reveal biologically distinct subtypes with distinct molecular and serum biomarker signatures. Two hundred PD patients and 121 healthy controls underwent structural MRI. Subject-specific cortical similarity networks were constructed using Morphometric INverse Divergence (MIND), and subtypes were identified with HYDRA. Spatial patterns were linked to regional gene expression from the Allen Human Brain Atlas through partial least squares regression, followed by functional and cell-type enrichment analyses. Serum neurofilament light chain (NfL) and glial fibrillary acidic protein (GFAP) were quantified using single-molecule array assays. No significant MIND differences emerged when PD patients were analysed as a single group. HYDRA identified two subtypes (ARI = 0.85) with divergent cortical organization that only partially overlapped with conventional motor phenotypes. Cluster 1 exhibited temporo-parietal MIND increases associated with synaptic and oligodendroglial signatures, without serum biomarker associations. Cluster 2 showed widespread fronto-cingulate MIND reductions enriched for mitochondrial, lysosomal, and proteostatic pathways, including the KEGG Parkinson’s disease pathway, and these reductions correlated with higher serum NfL and GFAP. These findings reveal two biologically distinct PD subtypes with divergent molecular architecture and systemic neurodegeneration beyond conventional motor phenotyping. Full article

Background/Objectives: Adverse neurological events caused by imipenem are usually more frequent in patients with epilepsy. This study investigates the effects of imipenem on hippocampal neurogenesis, astroglial activation, and behaviour in animals with pro-epileptogenic alterations. Methods: Five-month-old Wistar rats were divided into four groups: control (CT), pentylenetetrazol (PTZ), imipenem-treated group (IM), and imipenem after PTZ-kindling (IM-PTZ). Epileptogenesis was induced by PTZ-kindling for 28 days, followed by 10 days of imipenem (40 mg/kg) or saline injections. Rats underwent memory and anxiety tests followed by immunohistochemical analyses of doublecortin (DCX) and glial fibrillary acidic protein (GFAP) in the hippocampus. Results: Both kindled groups displayed comparable impairments in spatial learning and working memory, while imipenem alone did not alter behaviour. The IM-PTZ group failed to reach control-level performance only in the final Morris Water Maze acquisition trials, suggesting a deficit in memory consolidation rather than a total loss of retention, as the probe trial remained comparable across all groups. Although PTZ increased anxiety-like behaviour, no locomotor differences were observed in open-field test, confirming cognitive impairments were not due to motor deficits. These behavioural changes mirrored distinct cellular alterations: while PTZ alone triggered a compensatory increase in DCX neuronal density and astrocytic branching, imipenem co-administration suppressed this neurogenic response, bringing DCX to baseline. Furthermore, combined treatment induced an uncoupling of astrocytic response, marked by increased astrocyte density and reduced process complexity in dentate hilus and Cornus Ammonis 3 (CA3). Conclusions: These results suggest that imipenem modulates the cellular substrate of the pre-sensitized brain, interfering with hippocampal plasticity and glial compensatory mechanisms, rather than directly driving further behavioural deterioration. Full article

Distinguishing seizures from other causes of transient loss of consciousness in the emergency department (ED) is challenging. This PRISMA-guided systematic review evaluated serum brain injury biomarkers for the acute diagnosis of seizures in adults. We searched PubMed and Web of Science for studies published between 2015 and 2025 and included 14 studies in which blood sampling occurred shortly after the event, reflecting the ED diagnostic window. Given the heterogeneity across studies, the overall certainty of the evidence was low. Neuron-specific enolase (NSE) and ubiquitin carboxyl-terminal hydrolase L1 (UCH-L1) were consistently elevated after epileptic seizures compared to healthy controls. NSE effectively differentiated seizures from syncope, while UCH-L1 and glial fibrillary acidic protein (GFAP) distinguished epileptic from psychogenic non-epileptic seizures (PNESs). Neurofilament light chain (NfL) remained stable after a single seizure but increased markedly in status epilepticus (SE). S100B and BDNF results were inconsistent. Although no single biomarker serves as a standalone test, NSE and UCH-L1 are promising complementary diagnostic tools for identifying epileptic seizures in adults. Furthermore, NfL is a strong candidate marker for SE, reflecting neuroaxonal injury. Larger prospective, standardized studies are needed before routine ED implementation. Full article

Introduction: Adult-onset Alexander disease (AOAD) is a rare astrocytopathy linked to the glial fibrillary acidic protein (GFAP) gene, which is known for its clinical heterogeneity and common misdiagnosis. In adults, it may present with bulbar dysfunction, pyramidal signs, ataxia, dysautonomia, cognitive decline, or parkinsonism, which often mimics atypical parkinsonian syndromes like multiple system atrophy (MSA). The purpose of this case series was to define practical clinical, radiological, and genetic cues for suspecting AOAD in adults with atypical parkinsonism, autonomic dysfunction, or paroxysmal focal symptoms, particularly when genetic findings are inconclusive. Case Presentation: Four patients, aged 40 to 59 years, had progressive and varied neurological symptoms, like gait disturbance, lower limb weakness, dysarthria, dysphagia, autonomic dysfunction, parkinsonism, cognitive decline, and paroxysmal focal deficits. Initial diagnoses were parkinsonian syndrome, stroke, transient ischemic attack (TIA), and MSA. Diagnostic Assessment and Intervention: Brain magnetic resonance imaging (MRI) in all patients showed characteristic lower brainstem abnormalities, particularly atrophy of the medulla oblongata and upper cervical spinal cord, consistent with the “tadpole sign.” GFAP sequencing identified one likely pathogenic variant (p.Arg70Trp) and three variants of uncertain significance: p.Glu122_Arg124del, p.Met415Ile, and p.Glu195Val. Management was mainly symptomatic; one patient showed significant motor improvement after repetitive transcranial magnetic stimulation (rTMS). Conclusions: AOAD should be considered in adults with parkinsonism-plus syndromes or unexplained combinations of bulbar symptoms, pyramidal signs, autonomic dysfunction, and cognitive decline. Recognizing the tadpole sign on MRI may improve diagnostic accuracy, particularly when genetic results are inconclusive. Full article

Patients with cerebrovascular disease frequently require concomitant antiplatelet and antiseizure therapy. However, experimental evidence regarding potential pharmacodynamic interactions between these medications remains limited. The present study investigated whether clopidogrel affects the anticonvulsant effects of valproic acid (VPA) or levetiracetam (LEV) in a pentylenetetrazol (PTZ)-induced seizure model. Forty-two male Wistar rats were randomly allocated to seven groups (n = 6/group): Control, PTZ, clopidogrel (CLP), VPA, LEV, VPA + CLP + PTZ, and LEV + CLP + PTZ. Electroencephalographic recordings, passive avoidance testing, histopathological examination, and glial fibrillary acidic protein (GFAP) immunohistochemistry were performed to evaluate seizure activity, behavioral performance, neuronal injury, and astroglial activation. Both VPA and LEV significantly reduced spike–wave discharge frequency and duration compared with the PTZ group (p < 0.05). Clopidogrel alone did not exhibit anticonvulsant activity, and co-administration with either VPA or LEV did not significantly alter electrophysiological, behavioral, histopathological, or GFAP-associated immunohistochemical outcomes. Overall, these findings indicate that clopidogrel did not significantly affect the anticonvulsant efficacy of VPA or LEV under the experimental conditions of this acute PTZ-induced seizure model. Full article

Chronic kidney disease is increasingly recognised as a systemic disorder with important neurological consequences, including cognitive impairment. However, the field remains challenging because CKD-related cognitive decline involves diverse uremic toxins, overlapping vascular, inflammatory, metabolic, endothelial, and neurodegenerative pathways, inconsistent cognitive screening practices, and no unified treatment strategy. Within this context, the kidney–brain axis provides a useful framework for integrating renal dysfunction, toxin retention, systemic inflammation, blood–brain barrier disruption, and cognitive vulnerability. Of these mechanisms, uremic neurotoxicity offers a biologically credible connection between compromised renal clearance and cerebral dysfunction. Retained solutes such as indoxyl sulfate, p-cresyl sulfate, indole-3-acetic acid, trimethylamine-N-oxide, urea, guanidino compounds, lanthionine, quinolinic acid, and homocysteine may induce endothelial injury, oxidative stress, neuroinflammation, mitochondrial dysfunction, excitotoxicity, and glial activation. Although these pathways are supported by experimental and translational studies, direct causal evidence in humans remains limited, and most clinical data should currently be interpreted as associative rather than definitive proof of causality. These processes converge on neuronal and synaptic vulnerability and may elucidate the distinctive cognitive profile associated with chronic kidney disease, particularly deficits in attention, processing speed, and executive function. This review summarizes the most recent evidence on the epidemiology and clinical phenotype of cognitive impairment in chronic kidney disease. It also discusses the molecular and cellular mechanisms of uremic neurotoxicity and examines new biomarkers of the kidney–brain axis, including neurofilament light chain, glial fibrillary acidic protein, brain-derived neurotrophic factor, tight junction proteins, and uremic toxins. However, these biomarkers remain insufficiently validated for routine clinical use, as their interpretation is complicated by reduced renal clearance, systemic inflammation, comorbid vascular disease, methodological heterogeneity, and the lack of longitudinal studies linking biomarker changes to cognitive outcomes. Therapeutic strategies targeting uremic toxins remain compelling from a mechanistic standpoint, but they are not yet fully developed in clinical practice. Subsequent research ought to amalgamate toxin profiling, cognitive phenotyping, neuroimaging, endothelial and inflammatory biomarkers, alongside patient-centered outcomes. Integrating cognitive assessment into nephrology care may enhance risk stratification, collaborative decision-making, and personalised management for patients with chronic kidney disease. Full article

Introduction: A subependymal giant cell astrocytoma (SEGA) is a benign tumor typically associated with tuberous sclerosis complex (TSC), an autosomal dominant syndrome. Case report: The patient, a 15-year-old male, presented with headaches, nausea, and visual obscurations, consistent with increased intracranial pressure. Neuroimaging identified a mass in the anterior left lateral ventricle causing unilateral obstruction at the foramen of Monro. During microsurgery, smears showed a low-grade glial tumor with a biphasic mix of elongated astrocytes and large epithelioid-to-gemistocyte-like cells. Gross total resection was achieved. On permanent sections, a tumor with large polygonal, ganglioid, and gemistocytic-like cells was seen. Nuclear pleomorphism, a feature of SEGA, was present. On immunohistochemistry, the tumor was positive for glial fibrillary acidic protein (GFAP), S100, and CD34, and the cells also displayed nuclear staining for TTF-1. A diagnosis of SEGA in the absence of clinical features of TSC was established; however, definitive classification as sporadic remains limited by the lack of molecular data. Conclusions: This case highlights the importance of evaluating intraventricular masses through the integration of lineage-specific immunohistochemical panels to prevent misclassification of pleomorphic giant cells as high-grade gliomas. Full article

Progression independent of relapse activity (PIRA) and smouldering multiple sclerosis (MS) represent major unmet challenges in contemporary MS care. Disability may accumulate independently of clinical relapses, driven in part by chronic compartmentalised inflammation behind a relatively intact blood–brain barrier and incompletely captured by conventional monitoring tools. This narrative review synthesises evidence across four complementary biomarker domains for detecting smouldering MS and PIRA: advanced MRI (paramagnetic rim lesions [PRLs], slowly expanding lesions, deep grey matter atrophy, quantitative susceptibility mapping); fluid biomarkers (serum glial fibrillary acidic protein [sGFAP], serum neurofilament light chain [sNfL]); retinal optical coherence tomography (ganglion cell–inner plexiform layer thinning); and digital health metrics (wearable accelerometry, digital Symbol Digit Modalities Test). In a single prospective cohort, combined elevation of sGFAP and sNfL conferred a 4.71-fold increased hazard for PIRA (HR 4.71; 95% CI 2.05–9.77); independent data suggest sGFAP may carry selectivity for progression beyond sNfL, although this remains to be confirmed. No single domain sufficiently characterises smouldering pathology. We therefore propose a hypothesis-generating Multimodal PIRA Score (MPS) as a conceptual validation scaffold intended to structure—rather than inform—prospective multicentre evaluation against a long-horizon disability endpoint. Harmonisation of acquisition protocols, reference ranges, and digital phenotyping algorithms remains a prerequisite. Full article

Epidemiological investigations have indicated that females are particularly susceptible to perfluorooctane sulfonate (PFOS)-induced cognitive impairment, yet the mechanisms underlying this sex-specific vulnerability remain obscure. Estrogen and estrogen receptor β (ERβ) signaling are essential for female brain function, but their role in PFOS-induced neurotoxicity has not been explored. We therefore hypothesized that disruption of astrocyte-derived estrogen–ERβ signaling, leading to downregulation of N-myc downstream-regulated gene 2 (NDRG2) and subsequent synaptic dysfunction, contributes to PFOS-induced neurotoxicity in females. Female rats were exposed to PFOS for 30 days, followed by behavioral tests and hippocampal analysis. PC12 cells were treated with astrocyte-conditioned medium (ACM) to assess synaptic injury. Molecular docking was further performed to predict the binding affinity between PFOS and ERβ. In vivo, PFOS exposure impaired cognitive performance and caused hippocampal dysfunction, accompanied by decreased levels of estradiol (E2), aromatase (AROM), ERβ, N-myc downstream regulated gene 2 (NDRG2), and AMPA receptors (AMPARs), together with increased glial fibrillary acidic protein (GFAP) and Ca²⁺/calmodulin-dependent protein kinase II (CaMKII) in the hippocampus. In vitro, PFOS-exposed C6 cells showed reduced E2, AROM, ERβ, and NDRG2, along with elevated GFAP and extracellular glutamate concentration. PC12 cells treated with PFOS-ACM exhibited decreased synaptophysin (SYP), postsynaptic density protein 95 (PSD-95), and AMPARs, as well as increased CaMKII, indicative of synaptic injury. Pretreatment with E2 or the ERβ agonist diarylpropionitrile (DPN) could reverse these molecular alterations and mitigate neuronal dysfunction. Molecular docking revealed a strong binding affinity between PFOS and ERβ. Collectively, these findings support our hypothesis that PFOS impairs cognitive function in female rats by disrupting astrocyte-derived estrogen–ERβ–NDRG2 signaling, with NDRG2 as a potential downstream effector. This provides a mechanistic basis for the heightened female susceptibility to PFOS neurotoxicity and highlighting ERβ as a potential therapeutic target. Full article

Background/Objectives: This study aimed to perform analytical validation and evaluation of the clinical performance of the Access Glial Fibrillary Acidic Protein (GFAP) research-use-only (RUO) immunoassay (Beckman Coulter) in plasma. Methods: A fully automated GFAP immunoassay was developed and evaluated for analytical validity and clinical performance. Analytical validation assessed precision, sensitivity, linearity, analytical specificity, and the stability of calibrators and samples. Evaluation of predefined clinical performance criteria included method comparison against the Quanterix Simoa GFAP Advantage Plus (RUO) assay and assessment of GFAP levels between participants with Alzheimer’s disease (AD) and healthy controls. Results: The Access GFAP (RUO) immunoassay met all analytical criteria. Precision yielded coefficients of variation (CVs) < 10% across all concentration ranges. Sensitivity parameters included a lower limit of quantification (LLoQ) of 0.083 pg/mL and an analytical measurement range of 0.083–640 pg/mL. Linearity demonstrated <9% deviation across the measurement range. Interference testing showed <7% deviation for cross-reactants, common medications and AD-specific therapeutics. Plasma samples remained stable over 48 h at room temperature (<4% deviation) and five freeze–thaw cycles (<9% deviation). Method comparison demonstrated strong correlation with Simoa GFAP (R = 0.945) but systematic proportional bias, yielding 3% (slope = 0.030) of Simoa values. Samples from participants with AD exhibited significantly elevated GFAP levels (median 9.0 pg/mL, IQR: 5.3–19.1) versus controls (median 3.4 pg/mL, IQR: 1.5–6.5; p < 0.001). Conclusions: The high-throughput Access GFAP (RUO) immunoassay achieved all analytical performance criteria and demonstrated differences in GFAP levels between AD and healthy control sample cohorts. These findings support its use in research settings and as a foundation for future clinical implementation and may inform future studies evaluating cross-platform harmonization and potential clinical applications. Full article

The human olfactory bulb is a promising structure for the investigation of central nervous system disorders, including dementias of various etiologies. In Alzheimer’s disease, anosmia is among the earliest clinical manifestations. Although olfactory disturbances have also been reported in schizophrenia, alterations within the olfactory system remain insufficiently studied. The aim of this study was to identify changes in the olfactory bulbs of patients with schizophrenia. Olfactory bulbs obtained from patients with schizophrenia (n = 23) and individuals without identified nervous system pathology (n = 23) were examined. Patients with schizophrenia demonstrated a statistically significant decrease in the immunoreactive area of myelin basic protein and a significant increase in the immunoreactive area of glial fibrillary acidic protein compared with the control group. In addition, the thickness of the layer of incoming olfactory nerve fibers was significantly reduced in the schizophrenia group. Overall, our findings demonstrate neuroglial alterations in the human olfactory bulb in schizophrenia. Together with observations from other brain regions, these results may indicate that the identified changes are systemic rather than localized in nature. Full article

Blood-based biomarkers offer a promising “biochemical imaging” approach for acute ischemic stroke (AIS) management, providing objective and accessible tools to complement conventional neuroimaging. This narrative review synthesizes recent advances in biomarkers derived from multiple neurovascular unit (NVU) compartments, including glial fibrillary acidic protein (GFAP), S100 calcium-binding protein B (S100B), ubiquitin carboxy-terminal hydrolase L1 (UCH-L1), neuron-specific enolase (NSE), neurofilament light chain (NfL), matrix metalloproteinase-9 (MMP-9), Claudin-5, Occludin, brain-derived neurotrophic factor (BDNF), interleukin-33 (IL-33), tumor necrosis factor-alpha (TNF-alpha), PARK7/DJ-1, glycogen phosphorylase BB (GP-BB), and circulating microRNAs. We focus on their stage-specific clinical utility across three scenarios: (1) ultra-early differentiation between ischemic stroke and intracerebral hemorrhage in prehospital and emergency settings; (2) dynamic prediction and monitoring of hemorrhagic transformation after reperfusion therapies; and (3) assessment of infarct burden, neurorepair potential, and long-term functional outcomes. Despite their promise, clinical translation remains hindered by assay platform heterogeneity, lack of standardized cut-off values, limited cost-effectiveness data, and insufficient prospective validation adjusted for key covariates such as age and renal function. We further discuss multi-marker panel construction, including strategies to address biomarker collinearity and overfitting. Future directions emphasize stage-specific panels, point-of-care testing devices, and artificial intelligence algorithms to advance precision medicine in stroke care. Full article

Background: Patients with mild traumatic brain injury (mTBI) have a small but clinically relevant risk of intracranial injury (ICI), requiring timely detection. Computed tomography (CT) remains the diagnostic gold standard but is costly and exposes patients to ionising radiation. Combining blood-based biomarkers, glial fibrillary acidic protein (GFAP) and ubiquitin carboxy-terminal hydrolase L1 (UCH-L1), with clinical decision rules may allow safe exclusion of ICI without CT, reducing unnecessary imaging, radiation exposure, and resource use. Methods: A systematic review of clinical and economic studies in patients with mTBI was registered in PROSPERO (CRD420251051158). Searches were conducted in January 2025 and updated in May 2025 in MEDLINE, Embase, and the Cochrane Library. The aim was to assess the diagnostic accuracy and economic value of the combination of GFAP and UCH-L1 compared with CT scanning to rule out ICI in both adults and children with mTBI. Where available, studies directly comparing GFAP and UCH-L1 with S100β were also analysed descriptively. The quality of the clinical evidence was assessed with QUADAS-2 and GRADE. Meta-analyses used a bivariate random-effects model, with heterogeneity and sensitivity analyses explored. Results: Overall, 21 studies were considered in our review. Moderate- to high-quality evidence indicates that GFAP and UCH-L1, when used together with clinical assessment, have very high sensitivity and can reliably rule out ICI in adults with mTBI presenting within 12 h to the emergency department. Evidence for paediatric populations shows promise but remains very limited. Specificity is low, particularly in older adults, which limits the ability to reduce CT use in this high-risk group. Research on age-adjusted cut-offs is ongoing and may help to reduce the proportion of false positive tests without compromising sensitivity. Few studies directly compared GFAP and UCH-L1 with S100β, with slightly higher to equivalent sensitivity for GFAP and UCH-L1. Economic evaluations suggest possible cost savings and reduced CT utilisation, but these analyses rely on assumptions unsupported by robust data and are highly context-dependent. There is a lack of clarity in the included studies regarding whether existing clinical head rules were used to define the study populations (i.e., to determine which patients would be recommended for CT scanning) and, if so, which specific rules were applied. Conclusions: Evidence shows that GFAP and UCH-L1 can safely exclude ICI in adults with mTBI in whom a CT scan would otherwise be considered based on clinical assessment or decision rules. Nevertheless, real-world evidence and cost-effectiveness data are scarce. Further prospective studies, including paediatric and elderly populations, and integration with clinical decision rules will be informative to ensure optimal use in clinical practice. Full article

Background: Cognitive impairment is a common complication after ischemic stroke and affects patients’ quality of life. Elevated glial fibrillary acidic protein (GFAP) and low vitamin D levels may contribute to neuroinflammation and impaired neuroplasticity, but their association with post-stroke cognitive impairment remains unclear. This study aimed to determine whether high serum GFAP and low vitamin D levels are risk factors for cognitive impairment in ischemic stroke patients. Methods: A prospective cohort study was conducted in patients with acute ischemic stroke. Serum GFAP and vitamin D levels were measured on the third day after stroke onset using an enzyme-linked immunosorbent assay (ELISA). Cognitive function was assessed two weeks after stroke onset using the Indonesian version of the Montreal Cognitive Assessment (MoCA-Ina). Data were analyzed using the chi-square test and multivariate logistic regression. Results: Seventy-six subjects were included in this study, of which 55 (72.4%) developed cognitive impairment. High serum GFAP (≥1.885 ng/mL) (RR = 1.755; 95% CI: 1.252–2.459; p = 0.001) and low vitamin D levels (<16.185 ng/mL) (RR = 1.773; 95% CI: 1.234–2.547; p = 0.001) were both associated with cognitive impairment. Multivariate analysis showed that high GFAP (AOR = 10.039; 95% CI: 2.484–40.569; p = 0.001) and low vitamin D levels (AOR = 6.640; 95% CI: 1.798–24.518; p = 0.005) were independent risk factors. Conclusions: Elevated serum GFAP and low vitamin D levels were independently associated with cognitive impairment after ischemic stroke and may serve as potential biomarkers for early risk stratification. Full article