Dataset Information

Glial Fibrillary Acidic Protein and Ionized Calcium-Binding Adapter Molecule 1 Immunostaining Score for the Central Nervous System of Horses With Non-suppurative Encephalitis and Encephalopathies.

ABSTRACT: Like humans, horses are susceptible to neurotropic and neuroinvasive pathogens that are not always readily identified in histological sections. Instead, alterations in astrocytes and microglia cells can be used as pathological hallmarks of injured nervous tissue in a variety of infectious and degenerative diseases. On the other hand, equine glial cell alterations are poorly characterized in diseases. Therefore, in this study, we provide a statistically proved score system to classify astrogliosis and microgliosis in the central nervous system (CNS) of horses, based on morphological and quantitative analyses of 35 equine cases of encephalitis and/or encephalopathies and four non-altered CNS as controls. For this system, we used glial fibrillary acidic protein (GFAP) and ionized calcium-binding adapter molecule 1 (Iba1) immunohistochemistry, allied to statistical analysis to confirm that the scores were correctly designated. The scores of alterations ranged from 0 (non-altered) to 3 (severely altered) and provided a helpful method for describing astrocytic and microglial alterations in horses suffering from inflammatory and degenerative lesions. This system could be a template for comparative studies in other animal species and could aid algorithms designed for artificial intelligence methods lacking a defined morphological pattern.

SUBMITTER: Boos GS

PROVIDER: S-EPMC8299206 | biostudies-literature | 2021

REPOSITORIES: biostudies-literature

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Glial Fibrillary Acidic Protein and Ionized Calcium-Binding Adapter Molecule 1 Immunostaining Score for the Central Nervous System of Horses With Non-suppurative Encephalitis and Encephalopathies.

Boos Gisele Silva GS Failing Klaus K Colodel Edson Moleta EM Driemeier David D de Castro Márcio Botelho MB Bassuino Daniele Mariath DM Diomedes Barbosa José J Herden Christiane C

Frontiers in veterinary science 20210709

Like humans, horses are susceptible to neurotropic and neuroinvasive pathogens that are not always readily identified in histological sections. Instead, alterations in astrocytes and microglia cells can be used as pathological hallmarks of injured nervous tissue in a variety of infectious and degenerative diseases. On the other hand, equine glial cell alterations are poorly characterized in diseases. Therefore, in this study, we provide a statistically proved score system to classify astrogliosi ...[more]

PMID: 34307520

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Project description:IntroductionThere is a tremendous need for identifying reliable blood-based biomarkers for Alzheimer's disease (AD) that are tied to the biological ATN (amyloid, tau and neurodegeneration) framework as well as clinical assessment and progression.MethodsOne hundred forty-four elderly participants underwent 18F-AV45 positron emission tomography (PET) scan, structural magnetic resonance imaging (MRI) scan, and blood sample collection. The composite standardized uptake value ratio (SUVR) was derived from 18F-AV45 PET to assess brain amyloid burden, and the hippocampal volume was determined from structural MRI scans. Plasma glial fibrillary acidic protein (GFAP), phosphorylated tau-181 (ptau-181), and neurofilament light (NfL) measured by single molecular array (SIMOA) technology were assessed with respect to ATN framework, genetic risk factor, age, clinical assessment, and future functional decline among the participants.ResultsAmong the three plasma markers, GFAP best discriminated participants stratified by clinical diagnosis and brain amyloid status. Age was strongly associated with NfL, followed by GFAP and ptau-181 at much weaker extent. Brain amyloid was strongly associated with plasma GFAP and ptau-181 and to a lesser extent with plasma NfL. Moderate association was observed between plasma markers. Hippocampal volume was weakly associated with all three markers. Elevated GFAP and ptau-181 were associated with worse cognition, and plasma GFAP was the most predictive of future functional decline. Combining GFAP and ptau-181 together was the best model to predict brain amyloid status across all participants (AUC = 0.86) or within cognitively impaired participants (AUC = 0.93); adding NfL as an additional predictor only had a marginal improvement.ConclusionOur findings indicate that GFAP is of potential clinical utility in screening amyloid pathology and predicting future cognitive decline. GFAP, NfL, and ptau-181 were moderately associated with each other, with discrepant relevance to age, sex, and AD genetic risk, suggesting their relevant but differential roles for AD assessment. The combination of GFAP with ptau-181 provides an accurate model to predict brain amyloid status, with the superior performance of GFAP over ptau-181 when the prediction is limited to cognitively impaired participants.

Project description:Metachromatic leukodystrophy is a lethal metabolic leukodystrophy, with emerging treatments for early disease stages. Biomarkers to measure disease activity are required for clinical assessment and treatment follow-up. This retrospective study compared neurofilament light chain and glial fibrillary acidic protein (GFAP) levels in CSF (n = 11) and blood (n = 92) samples of 40 patients with metachromatic leukodystrophy (aged 0-42 years) with 38 neurologically healthy children (aged 0-17 years) and 38 healthy adults (aged 18-45 years), and analysed the associations between these levels with clinical phenotype and disease evolution in untreated and transplanted patients. Metachromatic leukodystrophy subtype was determined based on the (expected) age of symptom onset. Disease activity was assessed by measuring gross motor function deterioration and brain MRI. Longitudinal analyses with measurements up to 23 years after diagnosis were performed using linear mixed models. CSF and blood neurofilament light chain and GFAP levels in paediatric controls were negatively associated with age (all P < 0.001). Blood neurofilament light chain level at diagnosis (median, interquartile range; picograms per millilitre) was significantly increased in both presymptomatic (14.7, 10.6-56.7) and symptomatic patients (136, 40.8-445) compared to controls (5.6, 4.5-7.1), and highest among patients with late-infantile (456, 201-854) or early-juvenile metachromatic leukodystrophy (291.0, 104-445) and those ineligible for treatment based on best practice (291, 57.4-472). GFAP level (median, interquartile range; picogram per millilitre) was only increased in symptomatic patients (591, 224-1150) compared to controls (119, 78.2-338) and not significantly associated with treatment eligibility (P = 0.093). Higher blood neurofilament light chain and GFAP levels at diagnosis were associated with rapid disease progression in late-infantile (P = 0.006 and P = 0.051, respectively) and early-juvenile patients (P = 0.048 and P = 0.039, respectively). Finally, blood neurofilament light chain and GFAP levels decreased during follow-up in untreated and transplanted patients but remained elevated compared with controls. Only neurofilament light chain levels were associated with MRI deterioration (P < 0.001). This study indicates that both proteins may be considered as non-invasive biomarkers for clinical phenotype and disease stage at clinical assessment, and that neurofilament light chain might enable neurologists to make better informed treatment decisions. In addition, neurofilament light chain holds promise assessing treatment response. Importantly, both biomarkers require paediatric reference values, given that their levels first decrease before increasing with advancing age.

Dataset Information

Glial Fibrillary Acidic Protein and Ionized Calcium-Binding Adapter Molecule 1 Immunostaining Score for the Central Nervous System of Horses With Non-suppurative Encephalitis and Encephalopathies.

Publications

Glial Fibrillary Acidic Protein and Ionized Calcium-Binding Adapter Molecule 1 Immunostaining Score for the Central Nervous System of Horses With Non-suppurative Encephalitis and Encephalopathies.

Similar Datasets

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