Blood-based biomarkers of neuroaxonal and astroglial injury identify ultra-treatment-resistant schizophrenia.

To determine expression levels of ubiquitin C-terminal hydrolase-L1 (UCH-L1) and serum glial fibrillary acidic protein (GFAP) in patients with acute cerebral infarction and their clinical significance. Methods: A total of 80 patients with acute cerebral infarction in Chongqing Cancer Hospital from January 2014 to February 2016 were enrolled as an observation group. Another 80 healthy people served as a control group. The expression levels of UCH-L1 and GFAP in the 2 groups were detected. Results: Sensibility and specificity for UCH-L1 and GFAP were 75.0%, 87.5% and 81.3%, 90.0%, respectively. Receiver operating characteristic curve areas of UCH-L1 and GFAP were 0.670 and 0.757, respectively. There were no significant significance in age, gender, drinking, smoke, diabetes, and hyperlipidemia in the 2 groups (P>0.05). High blood pressure rate in the observation group was higher than that in the control group (P<0.05). Spearson/Pearson analysis showed that serum UCH-L1 and GFAP levels were positively correlated with hypertension, but they were negatively correlated with sex, age, diabetes, hyperlipidemia, alcohol consumption, smoking, and other factors. General data at different time in the observation group was not statistically different (P>0.05). The expression levels of UCH-L1 and GFAP in the observation group was higher than that in the control group (P<0.05). UCH-L1 and GFAP levels at different time in the 2 groups were not statistically different (P>0.05). UCH-L1 and GFAP levels in the light, medium, and heavy groups were higher than those in the control group (P<0.05), while UCH-L1 and GFAP levels in the medium and heavy groups were higher than those in the light group (P<0.05). There was significant difference between levels of UCH-L1 or GFAP and infarction size at different time in the observation group (P<0.05). The results of Pearson correlation analysis showed that the levels of serum UCH-L1 and GFAP were positively correlated (r=0.634, P=0.001). Conclusion: The levels of serum UCH-L1 and GFAP are significantly increased at the early stage of acute cerebral infarction, and they have a certain correlation with the severity of cerebral infarction, which can provide a basis for early clinical diagnosis and treatment.

Glial fibrillary acidic protein (GFAP) and ubiquitin C-terminal hydrolase-L1 (UCH-L1) have been studied as potential biomarkers of mild traumatic brain injury (mTBI). We report the levels of GFAP and UCH-L1 in patients with acute orthopedic injuries without central nervous system involvement, and relate them to the type of extracranial injury, head magnetic resonance imaging (MRI) findings, and levels of GFAP and UCH-L1 in patients with CT-negative mTBI. Serum UCH-L1 and GFAP were longitudinally measured from 73 patients with acute orthopedic injury on arrival and on days 1, 2, 3, 7 after admission, and on the follow-up visit 3-10 months after the injury. The injury types were recorded, and 71% patients underwent also head MRI. The results were compared with those found in patients with CT-negative mTBI (n = 93). The levels of GFAP were higher in patients with acute orthopedic trauma than in patients with CT-negative mTBI (p = 0.026) on arrival; however, no differences were found on the following days. The levels of UCH-L1 were not significantly different between these two groups at any measured point of time. Levels of GFAP and UCH-L1 were not able to distinguish patients with CT-negative mTBI from patients with orthopedic trauma. Patients with orthopedic trauma and high levels of UCH-L1 or GFAP values may be falsely diagnosed as having a concomitant mTBI, predisposing them to unwarranted diagnostics and unnecessary brain imaging. This casts a significant doubt on the diagnostic value of GFAP and UCH-L1 in cases with mTBI.

Background: Friedreich’s ataxia (FRDA) is the most common autosomal recessive ataxia. Disease-modifying treatments are not available yet; however, several compounds are currently under investigation. As a result, there is a growing need for the identification of robust and easily accessible biomarkers for the monitoring of disease activity and therapeutic efficacy. The simultaneous measurement of multiple brain-derived proteins could represent a time- and cost-efficient approach for biomarker investigation in pathologically complex neurodegenerative diseases like FRDA.Objectives: To investigate the role of plasma neurofilament-light chain (NfL), glial fibrillary acidic protein (GFAP), total tau (t-tau) and ubiquitin C-terminal hydrolase L1(UCHL1) as biomarkers in FRDA. Additionally, NfL measurements derived from the novel multiplex assay were compared to those from an established NfL singleplex assay.Methods: In this study, an ultrasensitive Single molecule array (Simoa) 4-plex assay was used for the measurement of plasma NfL, GFAP, t-tau, and UCHL1 in 33 FRDA patients and 13 age-matched controls. Differences in biomarker concentrations between these groups were computed and associations with genetic and disease related parameters investigated. Additionally, the agreement between NfL measurements derived from the 4-Plex and an established Simoa NfL singleplex assay was assessed.Results: Mean plasma NfL, GFAP and UCHL1 levels were significantly higher in FRDA patients than in controls (NfL: p < 0.001; GFAP: p = 0.006, and UCHL1: p = 0.020). Conversely, there was no significant difference in concentrations of t-tau in the patient and control group (p = 0.236). None of the proteins correlated with the GAA repeat length or the employed measures of disease severity. The individual NfL values derived from the two assays showed a strong concordance (rc = 0.93). Although the mean difference of 1.29 pg/mL differed significantly from 0 (p = 0.006), regression analysis did not indicate the presence of a proportional bias.Conclusion: This is the first study demonstrating that NfL, GFAP, and UCHL1 levels are raised in FRDA, potentially reflecting ongoing neuronal degeneration and glial activation. Further studies are required to determine their role as marker for disease activity and progression. Furthermore, the novel 4-plex assay appears to be a valid tool to simultaneously measure brain-derived proteins at extremely low concentrations in the peripheral circulation.

Glial fibrillary acidic protein (GFAP) and ubiquitin C-terminal hydrolase-L1 (UCH-L1) are promising biomarkers of traumatic brain injury (TBI). We investigated the relation of the GFAP and UCH-L1 levels to the severity of TBI during the first week after injury. Plasma UCH-L1 and GFAP were measured from 324 consecutive patients with acute TBI and 81 control subject enrolled in a 2-center prospective study. The baseline measures included initial Glasgow Coma Scale (GCS), head computed tomographic (CT) scan at admission, and blood samples for protein biomarkers that were collected at admission and on days 1, 2, 3, and 7 after injury. Plasma levels of GFAP and UCH-L1 during the first 2 days after the injury strongly correlated with the initial severity of TBI as assessed with GCS. Additionally, levels of UCH-L1 on the seventh day after the injury were significantly related to the admission GCS scores. At admission, both biomarkers were capable of distinguishing mass lesions from diffuse injuries in CT, and the area under the curve of the receiver-operating characteristic curve for prediction of any pathological finding in CT was 0.739 (95% confidence interval, 0.636-0.815) and 0.621 (95% confidence interval, 0.517-0.713) for GFAP and UCH-L1, respectively. These results support the prior findings of the potential role of GFAP and UCH-L1 in acute-phase diagnostics of TBI. The novel finding is that levels of GFAP and UCH-L1 correlated with the initial severity of TBI during the first 2 days after the injury, thus enabling a window for TBI diagnostics with latency. AUC, area under the curveCI, confidence intervalED, emergency departmentGCS, Glasgow Coma ScaleGRAP, glial fibrillary acidic proteinIMPACT, International Mission for Prognosis and Clinical TrialROC, receiver-operating characteristicTBI, traumatic brain injuryTRACK-TBI, Transforming Research and Clinical Knowledge in Traumatic Brain InjuryUCH-L1, ubiquitin C-terminal hydrolase-L1.

Objective: There is a growing body of research aimed at identifying biological markers that could indicate traumatic cerebral deaths such as traumatic brain damage in the postmortem period. In the event of astrocytic and neuronal injury, glial fibrillary acidic protein (GFAP) and ubiquitin C-terminal hydrolase L1 (UCH-L1) are released into cerebrospinal fluid and blood. In the postmortem identification of traumatic brain injury, the present research explores the ability of GFAP and UCH-L1. Methods: Cerebrospinal fluid and blood samples were obtained from medicolegal autopsies, 17 cases with severe head trauma, 9 cases with the non-lethal head trauma group and 18 control cases. UCH-L1 and GFAP levels in postmortem cerebrospinal fluid and serum were determined from an enzyme-linked immunosorbent assay (ELISA). Results: GFAP level in cerebrospinal fluid and serum was 2.68±0.67 ng/ml and 0.79±0.92 ng/ml in the lethal head trauma group, 2.74±0.64 ng/ml and 1.05±0.68 ng/ml the non-lethal head trauma group and 2.49±0.55 ng/ml and 1.05±0.89 ng/ml in the control group, respectively. UCH-L1 level in cerebrospinal fluid and serum was 3.02±0.68 ng/ml and 2.69±0.77 ng/ml in the lethal head trauma group, 3.34±0.70 ng/ml and 2.59±0.65 ng/ml the non-lethal head trauma group and 3.28±0.33 ng/ml and 2.74±0.34 ng/ml in the control group, respectively. Elevated cerebrospinal fluid and serum UCH-L1 and GFAP levels were observed in all cases, although absence of statistically significant difference between the trauma and control groups (p&gt;0.05). Conclusion: Further studies are needed to assess whether postmortem serum and CSF GFAP and UCH-L1 concentrations increase regardless of the cause of death.

In patients with metastatic breast cancer (MBC), brain metastases (BM) are associated with high morbidity and mortality. However, there is no validated serum biomarker that accurately predicts BM occurrence in these patients, and the role of serum biomarkers for prognosis remains unclear. Here, we evaluated the association of neurofilament light chain (NfL), ubiquitin C-terminal hydrolase L1 (UCHL1), glial fibrillary acidic protein (GFAP) and tau serum levels with BM presence and prognosis in patients with MBC. In serum samples from patients with MBC with (n=100) and without BM (n=47), we measured the biomarker serum levels using single molecule array (Simoa) technology (Neurology-4-Plex assay). To evaluate their accuracy to identify patients with BM, we determined the receiver operating characteristic curve and the area under the curve (AUC) for each biomarker and calculated their sensitivity and specificity. The median serum levels of NfL, UCHL1, tau and GFAP were significantly higher in patients with BM. The AUC for GFAP (0.82, 95% confidence interval [CI] 0.75-0.88) was significantly higher than those of the other biomarkers considered independently. Using the medians as cutoff values, elevated serum levels of NfL, UCHL1, tau and GFAP were associated with BM in univariate analysis, but only high GFAP levels in multivariate analysis (odd ratio 23.4, 95% CI 6.8-80.5, P< .001). Elevated serum GFAP levels were independently associated with poor outcome. GFAP outperforms NfL, UCHL1 and tau as diagnostic and prognostic factor of BM in patients with MBC. These results must now be validated in an independent cohort of patients.

Persistent neurodisability is a known complication in paediatric survivors of cerebral malaria and severe malarial anaemia. Tau, ubiquitin C-terminal hydrolase-L1, neurofilament-light chain, and glial fibrillary acidic protein have proven utility as biomarkers that predict adverse neurologic outcomes in adult and paediatric disorders. In paediatric severe malaria, elevated tau is associated with mortality and neurocognitive complications. We aimed to investigate whether a multi-analyte panel including ubiquitin C-terminal hydrolase-L1, neurofilament-light chain, and glial fibrillary acidic protein can serve as biomarkers of brain injury associated with mortality and neurodisability in cerebral malaria and severe malarial anaemia. In a prospective cohort study of Ugandan children, 18 months to 12 years of age with cerebral malaria (n = 182), severe malarial anaemia (n = 158), and asymptomatic community children (n = 118), we measured admission blood levels of ubiquitin C-terminal hydrolase-L1, neurofilament-light chain, and glial fibrillary acidic protein. We investigated differences in biomarker levels, associations with mortality, blood–brain barrier integrity, neurodeficits and cognitive Z-scores in survivors up to 24-month follow-up. Admission ubiquitin C-terminal hydrolase-L1 levels were elevated &amp;gt;95th percentile of community children in 71 and 51%, and neurofilament-light chain levels were elevated &amp;gt;95th percentile of community children in 40 and 37% of children with cerebral malaria and severe malarial anaemia, respectively. Glial fibrillary acidic protein was not elevated in disease groups compared with controls. In cerebral malaria, elevated neurofilament-light chain was observed in 16 children who died in hospital compared with 166 survivors (P = 0.01); elevations in ubiquitin C-terminal hydrolase-L1 levels were associated with degree of blood–brain barrier disruption (P = 0.01); and the % predictive value for neurodeficits over follow-up (discharge, 6-, 12-, and 24 months) increased for ubiquitin C-terminal hydrolase-L1 (60, 67, 72, and 83), but not neurofilament-light chain (65, 68, 60, and 67). In cerebral malaria, elevated ubiquitin C-terminal hydrolase-L1 was associated with worse memory scores in children &amp;lt;5 years at malaria episode who crossed to over 5 years old during follow-up cognitive testing [β −1.13 (95% confidence interval −2.05, −0.21), P = 0.02], and elevated neurofilament-light chain was associated with worse attention in children ≥5 years at malaria episode and cognitive testing [β −1.08 (95% confidence interval −2.05, −1.05), P = 0.03]. In severe malarial anaemia, elevated ubiquitin C-terminal hydrolase-L1 was associated with worse attention in children &amp;lt;5 years at malaria episode and cognitive testing [β −0.42 (95% confidence interval −0.76, −0.07), P = 0.02]. Ubiquitin C-terminal hydrolase-L1 and neurofilament-light chain levels are elevated in paediatric cerebral malaria and severe malarial anaemia. In cerebral malaria, elevated neurofilament-light chain is associated with mortality whereas elevated ubiquitin C-terminal hydrolase-L1 is associated with blood–brain barrier dysfunction and neurodeficits over follow-up. In cerebral malaria, both markers are associated with worse cognition, while in severe malarial anaemia, only ubiquitin C-terminal hydrolase-L1 is associated with worse cognition.

BackgroundThe aetiology of Alzheimer’s Disease and Related dementias (ADRD) in a diverse context is complex, and clinical methods lack sensitivity and specificity due to overlapping symptoms. This underscores the need of novel serum biomarkers in diagnosis of dementia. Serum glial fibrillary acidic protein (GFAP) and neurofilament light chain (NfL) are non‐amyloid blood‐based biomarkers indicative of ongoing inflammatory and neurodegenerative process. We aimed to assess and validate their diagnostic value in patients with Alzheimer’s dementia (AD) and Frontotemporal dementia (FTD) spectrum disorders in the Indian context.MethodNinety‐nine participants recruited in the study underwent detailed neurocognitive assessment along with basic brain imaging. Quantitative determination of serum Glial fibrillary acidic protein (GFAP), neurofilament light chain (NfL), total‐tau and ubiquitin C‐terminal hydrolase L1 (UCHL1) were assessed using Simoa platform following a 2‐step digital immunoassay method as per manufacturer’s instructions using HD‐X analyser. Healthy controls (n=29), and participants with AD (n=28) and FTD spectrum disorders (n=42) diagnosed as per standard criteria were recruited.ResultMean age of the participants and healthy controls was 61.26 years (10.31) and 55.69 years (8.97), respectively. GFAP and NfL were significantly higher in participants with dementia compared to healthy controls (p&lt;0.001). Serum GFAP levels were higher in AD (p&lt;0.001), while NfL levels were significantly elevated in AD and FTD compared to controls (p&lt; 0.05). However, there was no difference in t‐tau and UCHL1 levels between dementia group and healthy controls. Higher biomarkers levels of serum GFAP, NfL, t‐tau and UCHL1 were significantly associated with increasing levels of severity of dementia (r=0.539, p=0.000; r=0.637, p=0.000; r=0.241, p=0.016; r=0.476, p=0.000; respectively).ConclusionLevels of GFAP and NfL in serum have an emerging role in differentiating ADRD (AD and FTD) from healthy controls. These biomarkers are valuable predictors of severity across the neurodegenerative dementias. Further prospective cohort studies are required to replicate these findings in a diverse context.

This study set out to investigate the relationship between serum neurofilament light chain (NFL), glial fibrillary acidic protein (GFAP), and various non-motor symptoms (NMSs) in patients with Parkinson's disease (PD). The study included 37 healthy controls (HCs) and 51 PD patients. Clinical assessments of PD symptoms were conducted for all PD patients. The NMSS was utilised to evaluate the NMS burden (NMSB) in individuals. Based on the severity of NMSB, we further categorised the PD group into two subgroups: mild-moderate NMSB group and severe-very severe NMSB group. The amounts of NFL and GFAP in the serum were measured using an extremely sensitive single molecule array (Simoa) method. Statistical analyses were performed on the collected data using SPSS 26.0 and R (version 3.6.3). Serum GFAP and NFL levels in the PD group with severe-very severe NMSB were significantly higher than those in the mild-moderate NMSB group (GFAP: P < 0.007; NFL: P < 0.009). Serum NFL and GFAP levels had positive correlations with NMSS total scores (GFAP: r = 0.326, P = 0.020; NFL: r = 0.318, P = 0.023) and multiple subdomains. The relationship between the attention/memory domains of NMSS and NFL levels is significantly positive (r = 0.283, P = 0.044). Similarly, the mood/apathy domains of NMSS are also significantly positively correlated with GFAP levels (r = 0.441, P = 0.001). Patients with emotional problems or cognitive impairment had higher GFAP or NFL levels, respectively. Furthermore, it has been demonstrated that NMSs play a mediating role in the quality of life of patients with PD. Moreover, the combination of NFL and GFAP has proven to be more effective than using a single component in identifying PD patients with severe-very severe NMSB. The severity of NMSs in PD patients, particularly cognitive and emotional symptoms, was found to be associated with the levels of serum NFL and GFAP. This study marks the first attempt to examine the connection between NMSs of PD and the simultaneous identification of NFL and GFAP levels.

A diagnosis of traumatic brain injury (TBI) is typically based on patient medical history, a clinical examination, and imaging tests. Elevated plasma levels of glial fibrillary acidic protein (GFAP), ubiquitin c-terminal hydrolase L1 (UCH-L1), and neurofilament light chain (NFL) have been observed in numerous studies of TBI patients. It is reasonable to view traumatic optic neuropathy (TON) as a focal form of TBI. The purpose of this study was to assess if circulating GFAP, UCH-L1, and NFL are also elevated in a porcine model of TON. Serum levels of GFAP, UCH-L1, and NFL were measured immediately before optic nerve crush and 1 h post-injury in 10 Yucatan minipigs. Severity of optic nerve crush was confirmed by visual inspection of the optic nerve at time of injury, loss of visual function as measured by flash visual evoked potential (fVEP) at 7 and 14 days, and histological analysis of axonal transport of cholera toxin-β (CT-β) within the optic nerve. Post-crush concentrations of GFAP, UCH-L1, and NFL were all significantly elevated compared with pre-crush concentrations (p < 0.01, p = 0.01, and p < 0.01, respectively). The largest increase was observed for GFAP with the post-injury median concentration increasing nearly sevenfold. The use of these TBI biomarkers for diagnosing and managing TON may be helpful for non-ophthalmologists in particular in diagnosing this condition. In addition, the potential utility of these biomarkers for diagnosing other optic nerve and/or retinal pathologies should be evaluated.

Traumatic brain injury (TBI) results in neuronal, axonal and glial damage. Interventions targeting neuroinflammation to enhance recovery from TBI are needed. Exercise is known to improve cognitive function in TBI patients. Omega-3 fatty acids and vitamin D reportedly reduce inflammation, and in combination, might improve TBI outcomes. This study examined how an anti-inflammatory diet affected plasma TBI biomarkers, voluntary exercise and behaviors following exposure to mild TBI (mTBI). Adult, male rats were individually housed in cages fitted with running wheels and daily running distance was recorded throughout the study. A modified weight drop method induced mTBI, and during 30 days post-injury, rats were fed diets supplemented with omega-3 fatty acids and vitamin D3 (AIDM diet), or non-supplemented AIN-76A diets (CON diet). Behavioral tests were periodically conducted to assess functional deficits. Plasma levels of Total tau (T-tau), glial fibrillary acidic protein (GFAP), ubiquitin c-terminal hydrolase L1 (UCH-L1) and neurofilament light chain (NF-L) were measured at 48 h, 14 days, and 30 days post-injury. Fatty acid composition of food, plasma, and brain tissues was determined. In rats exposed to mTBI, NF-L levels were significantly elevated at 48 h post-injury (P < 0.005), and decreased to levels seen in uninjured rats by 14 days post-injury. T-tau, GFAP, and UCH-L1 plasma levels did not change at 48 h or 14 days post-injury. However, at 30 days post-injury, T-tau, GFAP and UCH-L1 all significantly increased in rats exposed to mTBI and fed CON diets (P < 0.005), but not in rats fed AIDM diets. Behavioral tests conducted post-injury showed that exercise counteracted cognitive deficits associated with mTBI. The AIDM diets significantly increased docosahexaenoic acid levels in plasma and brain tissue (P < 0.05), and in serum levels of vitamin D (P < 0.05). The temporal response of the four injury biomarkers examined is consistent with studies by others demonstrating acute and chronic neural tissue damage following exposure to TBI. The anti-inflammatory diet significantly altered the temporal profiles of plasma T-tau, GFAP, and UCH-L1 following mTBI. Voluntary exercise protected against mTBI-induced cognitive deficits, but had no impact on plasma levels of neurotrauma biomarkers. Thus, the prophylactic effect of exercise, when combined with an anti-inflammatory diet, may facilitate recovery in patients with mTBI.

Neurotrauma is the leading cause of death in individuals <45 years old. Many of the published articles on UCHL1 and GFAP lack rigorous methods and reporting. Due to the high heterogeneity between studies, we evaluated blood GFAP and UCHL1 levels in the same subjects. We determined the biomarker congruence among areas under the ROC curves (AUCs), sensitivities, specificities, and laboratory values in ng/L to avoid spurious results. The definitive meta-analysis included 1,880 subjects in eight studies. The items with the highest risk of bias were as follows: cut-off not prespecified and case-control design not avoided. The AUC of GFAP was greater than the AUC of UCHL1, with a lower prediction interval (PI) limit of 50.1 % for GFAP and 37.3 % for UCHL1, and a significantly greater percentage of GFAP Sp. The PI of laboratory results for GFAP and UCHL1 were 0.517-7,518 ng/L (diseased), 1.2-255 ng/L (nondiseased), and 3-4,180 vs. 3.2-1,297 ng/L, respectively. Only the GFAP positive cut-off (255 ng/L) appears to be reliable. The negative COs appear unreliable. GFAP needs better standardization. However, the AUCs of the phospho-Tau and phospho-Tau/Tau proteins resulted not significantly lower than AUC of GFAP, but this result needs further verifications.

Laboratory tests to diagnose neurosyphilis using cerebrospinal fluid (CSF) are currently disadvantageous as a lumbar puncture is required, which may result in patients with neurosyphilis missing an opportunity for early diagnosis. Thus, blood biomarker candidates that are more convenient and minimally invasive to collect for diagnosing neurosyphilis is urgently needed. This observational study aimed to analyze serum ubiquitin C-terminal hydrolase-L1 (UCH-L1), glial fibrillary acidic protein (GFAP), and neurofilament light chain (NF-L) levels in 153 patients without human immunodeficiency virus (HIV) and to evaluate their diagnostic performance in neurosyphilis compared with CSF. Serum UCH-L1, GFAP, and NF-L levels were significantly higher in patients with neurosyphilis compared with patients with uncomplicated syphilis or non-syphilis. For the diagnosis of neurosyphilis, serum UCH-L1, GFAP, and NF-L revealed sensitivities of 90.20%, 80.40%, and 88.24%, and specificities of 92.16%, 78.43%, and 80.39%, respectively, at cutoff levels of 814.50 pg/mL, 442.70 pg/mL, and 45.19 pg/mL, respectively. In patients with syphilis, serum UCH-L1, GFAP, and NF-L levels correlated strongly or moderately with those in the CSF, with similar or better diagnostic performance than those in the CSF. The testing algorithms' sensitivity and specificity increased to 98.04% and 96.08%, respectively, when subjected to parallel and combination testing, respectively. To avoid lumbar puncture, each serum UCH-L1, GFAP, and NF-L is a good entry point and biomarker candidate for the diagnosis of neurosyphilis among patients without HIV. These proteins used in concerto can further improve the diagnostic sensitivity and specificity.

The rising dementia burden and limited knowledge of fluid biomarkers in South Asians highlights this study's aim on evaluating their utility for the diagnosis of Alzheimer's disease and related dementias (ADRD). Participants with ADRD were recruited from a cognitive disorders clinic in India. We performed cognitive assessments and severity evaluations using standard tests. Serum and cerebrospinal fluid (CSF) levels of glial fibrillary acidic protein (GFAP), neurofilament light chain (NfL), total tau, and ubiquitin C-terminal hydrolase L1 (UCHL1) were quantified using a Simoa HD analyzer. Among the 101 participants, serum GFAP and NfL levels were significantly greater in dementia participants (n=70) than controls. Serum biomarkers significantly correlated with their corresponding CSF levels. Significant correlations were noted for serum and CSF GFAP and NfL in Alzheimer's disease (ρ=0.492, 0.664) and between serum and CSF NfL in frontotemporal dementia (ρ=0.727). Serum GFAP, NfL, and UCHL1 demonstrated high diagnostic accuracy (area under the curve =0.765-0.806). Our results emphasize the role of fluid biomarkers in diagnosing dementia in low-resource settings in South Asians. Serum glial fibrillary acidic protein (GFAP) and neurofilament light chain (NfL) levels were significantly greater in patients with dementia than in healthy controls.Significant correlation was observed between the serum and cerebrospinal fluid levels of GFAP, NfL, and total tau independent of the baseline demographics or co-morbidities, indicating their potential role in clinical practice.Serum biomarker levels were related to the severity of dementia.This is one of few studies on fluid-based biomarkers in diverse cohorts with Alzheimer's disease and related dementias in the South Asian cohort with limited resources.

IntroductionThis study investigates the significance of glial fibrillary acidic protein (GFAP) and ubiquitin C-terminal hydrolase L1 (UCHL-1) in cerebrospinal fluid (CSF) of patients with multiple sclerosis (MS) and peripheral neuropathy (PN).MethodsWe included 41 MS patients, 35 PN patients, and 36 controls across 5 sites. MS patient data included lesion counts, disease activity, albumin quotient, and Expanded Disability Status Scale (EDSS) scores. PN patients included those with acute and chronic inflammatory demyelinating polyneuropathy and sensorimotor neuropathy based on nerve conduction studies. CSF concentrations of GFAP and UCHL-1 were measured using the MILLIPLEX Map Human Neuroscience Magnetic Bead Panel 1.ResultsBoth GFAP and UCHL-1 levels were significantly higher in the two patient groups compared to controls. In the MS group, GFAP showed a strong correlation with disease duration, EDSS score, non-enhancing lesions, and the CSF/blood albumin quotient. UCHL-1 levels were significantly higher in patients with active disease (gadolinium-enhancing lesions). The combination of UCHL-1 and GFAP improved diagnostic accuracy (AUC 0.895, 95% CI 0.780-1.000) compared to the independent measurement of either marker for indicating Gd-negative lesions. In the PN group, CSF GFAP levels were significantly lower in patients with purely demyelinating neuropathy compared to those with axonal or mixed neuropathy.ConclusionGFAP serves as a sensitive marker for axonal damage in PN, while UCHL-1 closely correlates with disease activity in MS patients.