Evidence for reduced synaptic protein SNAP-25 in cerebrospinal fluid in major depressive disorder and schizophrenia.

Background: Decreased cerebrospinal fluid (CSF) levels of synaptic proteins, possibly reflecting impaired synaptic function, have been observed in major depressive disorder (MDD).

Objective: To investigate the diagnostic utility of the soluble N-ethylmaleimide-sensitive-factor attachment receptor (SNARE) complex protein, synaptosomal-associated protein of 25 kDa (SNAP-25), for MDD.

Methods: Overall, 208 participants with one of MDD, schizophrenia (SCZ) or bipolar disorder (BD), and healthy controls (HCs) were retrospectively enrolled.

Neurofilament light chain reference values in serum and cerebrospinal fluid: a bi-compartmental analysis in neurological diseases.

Background: Concentrations of neurofilament light chain (NfL), a neuroaxonal damage marker, increase with age. Therefore, age-dependent reference values are important in clinical practice. However, so far these have only been established with a bead-based system and age-dependent z-scores for CSF are missing.

Clinical use and reporting of neurofilament quantification in neurological disorders: A global overview.

Introduction: Neurofilament light chain (NfL) quantification aids in diagnosing and predicting neurological disorders, but clinical and laboratory practices vary across centers. Differences in result interpretation and reporting further challenge test commutability. This study aimed to review the global analytical and post-analytical methods used for NfL measurement in routine clinical practice across different contexts.

Diagnostic performance of plasma Aβ42/40 ratio, p-tau181, GFAP, and NfL along the continuum of Alzheimer's disease and non-AD dementias: An international multi-center study.

Introduction: Plasma phosphorylated tau (p-tau)181, glial fibrillary acidic protein (GFAP), neurofilament light chain (NfL), and amyloid beta ratio (Aβ42/40) may have diagnostic and prognostic value in Alzheimer's disease (AD). Here we assess which markers can best identify AD from controls and other non-AD dementias in a large international multi-center study.

Methods: Plasma samples (n = 1298) were collected from six international centers.

Biomarkers in Aneurysmatic and Spontaneous Subarachnoid Haemorrhage: A Clinical Prospective Multicentre Biomarker Panel Study of S100B, Claudin-5, Interleukin-10, TREM-1, TREM-2 and Neurofilament Light Chain As Well As Immunoglobulin G and M.

Following aneurysmatic subarachnoid haemorrhage (SAH), complex pathophysiological processes take place which result in ischaemia, dysfunction of the blood-brain barrier and the clinical development of vasospasms and delayed cerebral ischaemia (DCI). The aim of this study was to present a biomarker panel that can be used for temporal assignment in the pathophysiological process after haemorrhage, a prediction of vasospasm, DCI or outcome. In a prospective multicentre approach, complex laboratory chemistry tests were used to determine the value of the biomarkers S100B, Claudin-5, Interleukin (IL) -10, Triggering receptor expresses on myeloid cells (TREM)-1 and TREM-2, and neurofilament light chain (NfL) as well as IgG and IgM in plasma and Cerebro-spinal-fluid (CSF) in SAH patients.

Phosphorylated tau 181 and 217 are elevated in serum and muscle of patients with amyotrophic lateral sclerosis.

Blood phosphorylated (p)-tau 181 and p-tau 217 have been proposed as accurate biomarkers of Alzheimer's disease (AD) pathology. However, blood p-tau 181 is also elevated in amyotrophic lateral sclerosis (ALS) without a clearly identified source. We measured serum p-tau 181 and p-tau 217 in a multicentre cohort of ALS (n = 152), AD (n = 111) cases and disease controls (n = 99) recruited from four different centres.

Increased plasma DOPA decarboxylase levels in Lewy body disorders are driven by dopaminergic treatment.

DOPA Decarboxylase (DDC) has been proposed as a cerebrospinal fluid (CSF) biomarker with increased concentrations in Lewy body disorders (LBDs) and highest levels in patients receiving dopaminergic treatment. Here we evaluate plasma DDC, measured by proximity extension assay, and the effect of dopaminergic treatment in three independent LBD (with a focus on dementia with Lewy bodies (DLB) and Parkinson's disease (PD)) cohorts: an autopsy-confirmed cohort (n = 71), a large multicenter, cross-dementia cohort (n = 1498) and a longitudinal cohort with detailed treatment information (n = 66, median follow-up time[IQR] = 4[4, 4] years). Plasma DDC was not altered between different LBDs and other disease groups or controls in absence of treatment.

Prognostic serum biomarkers of synaptic, neuronal and glial injury in patients with acute ischemic stroke of the anterior circulation.

Background: We aimed to investigate the prognostic role of β-synuclein in comparison to that of neurofilament light chain (NfL) and glial fibrillary acidic protein (GFAP) for predicting functional outcome after acute ischemic stroke (AIS).

Methods: We measured serum concentrations of β-synuclein, NfL and GFAP 24 h after hospital admission in 213 consecutive patients with moderate-to-severe AIS. We investigated the association between serum biomarkers and radiological/clinical characteristics, 3-months mortality and functional outcome on the modified Rankin Scale (mRS).

CSF synaptic biomarkers and cognitive impairment in multiple sclerosis.

Background: People with multiple sclerosis (PwMS) experience various degrees of cognitive impairment (CI). Synaptic dysfunction may contribute to CI in PwMS but cerebrospinal fluid (CSF) synaptic biomarkers are unexplored in MS.

Objective: To assess the role of CSF synaptosomal-associated protein 25 (SNAP-25), β-synuclein, neurogranin and neurofilament light chain protein (NfL) in patients with early relapsing MS with and without CI.

Quantification of blood glial fibrillary acidic protein using a second-generation microfluidic assay. Validation and comparative analysis with two established assays.

Objectives: Increased levels of glial fibrillary acidic protein (GFAP) in blood have been identified as a valuable biomarker for some neurological disorders, such as Alzheimer's disease and multiple sclerosis. However, most blood GFAP quantifications so far were performed using the same bead-based assay, and to date a routine clinical application is lacking.

Methods: In this study, we validated a novel second-generation (2nd gen) Ella assay to quantify serum GFAP.

Serum β-synuclein, neurofilament light chain and glial fibrillary acidic protein as prognostic biomarkers in moderate-to-severe acute ischemic stroke.

We aimed to assess the prognostic value of serum β-synuclein (β-syn), neurofilament light chain (NfL) and glial fibrillary acidic protein (GFAP) in patients with moderate-to-severe acute ischemic stroke. We measured β-syn, GFAP and NfL in serum samples collected one day after admission in 30 adult patients with moderate-to-severe ischemic stroke due to middle cerebral artery (MCA) occlusion. We tested the associations between biomarker levels and clinical and radiological scores (National Institute of Health Stroke Scale scores, NIHSS, and Alberta Stroke Program Early CT Score, ASPECTS), as well as measures of functional outcome (modified Rankin Scale, mRS).

Development and multi-center validation of a fully automated digital immunoassay for neurofilament light chain: toward a clinical blood test for neuronal injury.

Objectives: Neurofilament light chain (NfL) has emerged as a promising biomarker for detecting and monitoring axonal injury. Until recently, NfL could only be reliably measured in cerebrospinal fluid, but digital single molecule array (Simoa) technology has enabled its precise measurement in blood samples where it is typically 50-100 times less abundant. We report development and multi-center validation of a novel fully automated digital immunoassay for NfL in serum for informing axonal injury status.

Oral treatment with the all-d-peptide RD2 enhances cognition in aged beagle dogs - A model of sporadic Alzheimer's disease.

Disease-modifying therapies to treat Alzheimer's disease (AD) are of fundamental interest for aging humans, societies, and health care systems. Predictable disease progression in transgenic AD models favors preclinical studies employing a preventive study design with an early pre-symptomatic treatment start, instead of assessing a truly curative approach with treatment starting after diagnosed disease onset. The aim of this study was to investigate the pharmacokinetic profile and efficacy of RD2 to enhance short-term memory and cognition in cognitively impaired aged Beagle dogs - a non-transgenic model of truly sporadic AD.

Plasma β-synuclein, GFAP, and neurofilaments in patients with malignant gliomas undergoing surgical and adjuvant therapy.

We analyzed the longitudinal concentrations and prognostic roles of plasma β-synuclein (β-syn), glial fibrillary acidic protein (GFAP), and neurofilament proteins (NfL and NfH) in 33 patients with malignant gliomas, who underwent surgical and adjuvant therapy. GFAP and NfL levels were increased in patients with glioblastoma compared to cases with other tumors. β-syn, NfL and NfH increased after surgery, whereas GFAP decreased at long-term follow-up.

CSF Synaptic Biomarkers in AT(N)-Based Subgroups of Lewy Body Disease.

Background And Objectives: Patients with Lewy body disease (LBD) often show a co-occurring Alzheimer disease (AD) pathology. CSF biomarkers allow the detection in vivo of AD-related pathologic hallmarks included in the amyloid-tau-neurodegeneration (AT(N)) classification system. Here, we aimed to investigate whether CSF biomarkers of synaptic and neuroaxonal damage are correlated with the presence of AD copathology in LBD and can be useful to differentiate patients with LBD with different AT(N) profiles.

Higher plasma β-synuclein indicates early synaptic degeneration in Alzheimer's disease.

Introduction: β-Synuclein is an emerging synaptic blood biomarker for Alzheimer's disease (AD) but differences in β-synuclein levels in preclinical AD and its association with amyloid and tau pathology have not yet been studied.

Methods: We measured plasma β-synuclein levels in cognitively unimpaired individuals with positive Aβ-PET (i.e.

Development of an ultrasensitive microfluidic assay for the analysis of Glial fibrillary acidic protein (GFAP) in blood.

A rapid and reliable detection of glial fibrillary acidic protein (GFAP) in biological samples could assist in the diagnostic evaluation of neurodegenerative disorders. Sensitive assays applicable in the routine setting are needed to validate the existing GFAP tests. This study aimed to develop a highly sensitive and clinically applicable microfluidic immunoassay for the measurement of GFAP in blood.

Blood β-synuclein is related to amyloid PET positivity in memory clinic patients.

Introduction: β-synuclein is an emerging blood biomarker to study synaptic degeneration in Alzheimer´s disease (AD), but its relation to amyloid-β (Αβ) pathology is unclear.

Methods: We investigated the association of plasma β-synuclein levels with flutemetamol positron emission tomography (PET) in patients with AD dementia (n = 51), mild cognitive impairment (MCI-Aβ+ n = 18, MCI- Aβ- n = 30), non-AD dementias (n = 22), and non-demented controls (n = 5).

Results: Plasma β-synuclein levels were higher in Aβ+ (AD dementia, MCI-Aβ+) than in Aβ- subjects (non-AD dementias, MCI-Aβ-) with good discrimination of Aβ+ from Aβ- subjects and prediction of Aβ status in MCI individuals.

Visinin-like protein 1 levels in blood and CSF as emerging markers for Alzheimer's and other neurodegenerative diseases.

Background: Visinin-like protein 1 (VILIP-1) belongs to the group of emerging biomarkers with the potential to support the early diagnosis of Alzheimer's disease (AD). However, studies investigating the differential diagnostic potential in cerebrospinal fluid (CSF) are rare and are not available for blood.

Methods: We set up a novel, sensitive single molecule array (Simoa) assay for the detection of VILIP-1 in CSF and serum.

Glutamate receptor 4 as a fluid biomarker for the diagnosis of psychiatric disorders.

Psychiatric disorders are widely underreported diseases, especially in their early stages. So far, there is no fluid biomarker to confirm the diagnosis of these disorders. Proteomics data suggest the synaptic protein glutamate receptor 4 (GluR4), part of the AMPA receptor, as a potential diagnostic biomarker of major depressive disorder (MDD).