External quality assessment performance in ten countries: an IFCC global laboratory quality project.

Objectives: This study aimed to assess the validity of external quality assessment (EQA) laboratory results across various cultural and environmental contexts and to identify potential improvement areas.

Methods: The International Federation of Clinical Chemistry and Laboratory Medicine (IFCC) Task Force on Global Laboratory Quality (TF-GLQ) conducted a 2-year study (2022 and 2023) in which EQA materials, related software and online training was provided by a commercial vendor to 100 laboratories in ten IFCC member society countries. The results were analysed on a monthly basis by the TF-GLQ, to show the number of submissions per country, tests per lab, acceptability rates, random failures and to get a measure of which analytes performed poorly.

European intersocietal recommendations for the biomarker-based diagnosis of neurocognitive disorders.

The recent commercialisation of the first disease-modifying drugs for Alzheimer's disease emphasises the need for consensus recommendations on the rational use of biomarkers to diagnose people with suspected neurocognitive disorders in memory clinics. Most available recommendations and guidelines are either disease-centred or biomarker-centred. A European multidisciplinary taskforce consisting of 22 experts from 11 European scientific societies set out to define the first patient-centred diagnostic workflow that aims to prioritise testing for available biomarkers in individuals attending memory clinics.

Early brain metabolic disturbances associated with delayed cerebral ischemia in patients with severe subarachnoid hemorrhage.

Delayed cerebral ischemia (DCI) is a devastating complication of aneurysmal subarachnoid hemorrhage (ASAH) causing brain infarction and disability. Cerebral microdialysis (CMD) monitoring is a focal technique that may detect DCI-related neurochemical changes as an advance warning. We conducted retrospective analyses from 44 poor-grade ASAH patients and analyzed glucose, lactate, pyruvate, and glutamate concentrations in control patients without DCI (n = 19), and in patients with DCI whose CMD probe was located within (n = 17) or outside (n = 8) a new infarct.

External quality assessment practices in medical laboratories: an IFCC global survey of member societies.

Objectives: Clinical laboratory results are required for critical medical decisions, underscoring the importance of quality results. As part of total quality management, external quality assessment (EQA) is a vital component to ensure laboratory accuracy. The goal of this survey was to evaluate the current status of global laboratory quality systems and assess the need for implementation, expansion, or harmonization of EQA programs (EQAP) for Clinical Chemistry and Laboratory Medicine.

Prion strains associated with iatrogenic CJD in French and UK human growth hormone recipients.

Treatment with human pituitary-derived growth hormone (hGH) was responsible for a significant proportion of iatrogenic Creutzfeldt-Jakob disease (iCJD) cases. France and the UK experienced the largest case numbers of hGH-iCJD, with 122 and 81 cases respectively. Differences in the frequency of the three PRNP codon 129 polymorphisms (MM, MV and VV) and the estimated incubation periods associated with each of these genotypes in the French and the UK hGH-iCJD cohorts led to the suggestion that the prion strains responsible for these two hGH-iCJD cohorts were different.

Prion potentiation after life-long dormancy in mice devoid of PrP.

Prions are neurotropic pathogens composed of misfolded assemblies of the host-encoded prion protein PrP which replicate by recruitment and conversion of further PrP by an autocatalytic seeding polymerization process. While it has long been shown that mouse-adapted prions cannot replicate and are rapidly cleared in transgenic PrP mice invalidated for PrP, these experiments have not been done with other prions, including from natural resources, and more sensitive methods to detect prion biological activity. Using transgenic mice expressing human PrP to bioassay prion infectivity and RT-QuIC cell-free assay to measure prion seeding activity, we report that prions responsible for the most prevalent form of sporadic Creutzfeldt-Jakob disease in human (MM1-sCJD) can persist indefinitely in the brain of intra-cerebrally inoculated PrP mice.

DAMPs and RAGE Pathophysiology at the Acute Phase of Brain Injury: An Overview.

Early or primary injury due to brain aggression, such as mechanical trauma, hemorrhage or is-chemia, triggers the release of damage-associated molecular patterns (DAMPs) in the extracellular space. Some DAMPs, such as S100B, participate in the regulation of cell growth and survival but may also trigger cellular damage as their concentration increases in the extracellular space. When DAMPs bind to pattern-recognition receptors, such as the receptor of advanced glycation end-products (RAGE), they lead to non-infectious inflammation that will contribute to necrotic cell clearance but may also worsen brain injury.

Differential diagnostic value of total alpha-synuclein assay in the cerebrospinal fluid between Alzheimer's disease and dementia with Lewy bodies from the prodromal stage.

Background: Several studies have investigated the value of alpha-synuclein assay in the cerebrospinal fluid (CSF) of Alzheimer's disease (AD) and dementia with Lewy bodies (DLB) patients in the differential diagnosis of these two pathologies. However, very few studies have focused on this assay in AD and DLB patients at the MCI stage.

Methods: All patients were enrolled under a hospital clinical research protocol from the tertiary Memory Clinic (CM2R) of Alsace, France, by an experienced team of clinicians.

Significance and Diagnostic Accuracy of Early S100B Serum Concentration after Aneurysmal Subarachnoid Hemorrhage.

Background: Early brain injuries (EBI) are one of the most important causes of morbidity and mortality after subarachnoid hemorrhage. At admission, a third of patients are unconscious (spontaneously or sedated) and EBI consequences are not evaluable. To date, it is unclear who will still be comatose (with severe EBI) and who will recover (with less severe EBI) once the aneurysm is treated and sedation withdrawn.

A combination of total tau and neurofilaments discriminates between neurodegenerative and primary psychiatric disorders.

Background And Purpose: Neuropsychiatric symptoms are commonly observed in neurodegenerative diseases. No biomarker is currently available to diagnose psychiatric conditions. As a consequence, the distinction between psychiatric and neurodegenerative disorders can be challenging in daily practice.

The standardization of cerebrospinal fluid markers and neuropathological diagnoses brings to light the frequent complexity of concomitant pathology in Alzheimer's disease: The next challenge for biochemical markers?

During the last two decades, neuropathological examination of the brain has evolved both technically and scientifically. The increasing use of immunohistochemistry to detect protein aggregates paralleled a better understanding of neuroanatomical progression of protein deposition. As a consequence, an international effort was achieved to standardize hyperphosphorylated-Tau (phospho-TAU), ßAmyloid (Aß), alpha syncuclein (alpha-syn), phosphorylated transactive response DNA-binding protein 43 (phospho-TDP43) and vascular pathology detection.

Development of an automated capillary nano-immunoassay-Simple Western assay-to quantify total TDP43 protein in human platelet samples.

Frontotemporal lobar degeneration syndrome is the second cause of young-onset dementia. Unfortunately, reliable biomarkers are currently lacking for the diagnosis of this disease. As TDP43 protein is one of the proteins pathologically involved in frontotemporal lobar degeneration, many studies have been performed to assess TDP43 protein diagnostic performances.

France Will No More Reimburse Available Symptomatic Drugs Against Alzheimer's Disease.

The French Minister of Health published a decree on May 29th of 2018 removing the drugs used to fight against symptoms due to Alzheimer's disease (donepezil, rivastigmine, galantamine, memantine) from the list of available reimbursed drugs. This follows the advice delivered by the High Authority for Health in 2016 and 2018 stating an "insufficient medical benefit and dangerousness because of significant side effects". The main French scientific and medical societies and professional associations want to state here their deep disagreement regarding this unfair decision.

C9orf72 Protein Plasmatic Concentrations Are Similar between C9ORF72 Expansion Carriers and Noncarriers in Frontotemporal Dementia.

Background/aims: The aim of the study was to assess the theory of haploinsufficiency in C9ORF72 expansion carriers, the most frequent causative gene of frontotemporal dementia.

Methods: Plasmatic concentrations of C9orf72 protein were measured in 33 patients suspected of familial frontotemporal dementia using an enzyme-linked immunosorbent assay.

Results: No difference was observed between C9ORF72 expansion carriers (21.

Isotopic Evidence for Disrupted Copper Metabolism in Amyotrophic Lateral Sclerosis.

Redox-active metals are thought to be implicated in neurodegenerative diseases including amyotrophic lateral sclerosis (ALS). To address this point, we measured the concentrations of 12 elements and, for the first time, the stable isotope compositions of copper (redox-active) and zinc (redox-inactive) in human cerebrospinal fluids of 31 patients with ALS, 11 age-matched controls (CTRL), and 14 patients with Alzheimer disease. We first show that metal concentrations weakly discriminate patients with ALS from the two other groups.

Amyloid-Beta Radiotracer [F]BF-227 Does Not Bind to Cytoplasmic Glial Inclusions of Postmortem Multiple System Atrophy Brain Tissue.

The accumulation of aggregated alpha-synuclein (-syn) in multiple brain regions is a neuropathological hallmark of synucleinopathies. Multiple system atrophy (MSA) is a synucleinopathy characterized by the predominant cerebral accumulation of aggregated -syn as cytoplasmic glial inclusions (CGI). A premortem diagnosis tool would improve early diagnosis and help monitoring disease progression and therapeutic efficacy.

White paper by the Society for CSF Analysis and Clinical Neurochemistry: Overcoming barriers in biomarker development and clinical translation.

Body fluid biomarkers have great potential for different clinical purposes, including diagnosis, prognosis, patient stratification and treatment effect monitoring. This is exemplified by current use of several excellent biomarkers, such as the Alzheimer's disease cerebrospinal fluid (CSF) biomarkers, anti-neuromyelitis optica antibodies and blood neurofilament light. We still, however, have a strong need for additional biomarkers and several gaps in their development and implementation should be filled.

Experimental transfusion of variant CJD-infected blood reveals previously uncharacterised prion disorder in mice and macaque.

Exposure of human populations to bovine spongiform encephalopathy through contaminated food has resulted in <250 cases of variant Creutzfeldt-Jakob disease (vCJD). However, more than 99% of vCJD infections could have remained silent suggesting a long-term risk of secondary transmission particularly through blood. Here, we present experimental evidence that transfusion in mice and non-human primates of blood products from symptomatic and non-symptomatic infected donors induces not only vCJD, but also a different class of neurological impairments.

Multicenter Analytical Validation of Aβ40 Immunoassays.

Background: Before implementation in clinical practice, biomarker assays need to be thoroughly analytically validated. There is currently a strong interest in implementation of the ratio of amyloid-β peptide 1-42 and 1-40 (Aβ42/Aβ40) in clinical routine. Therefore, in this study, we compared the analytical performance of six assays detecting Aβ40 in cerebrospinal fluid (CSF) in six laboratories according to a recently standard operating procedure (SOP) developed for implementation of ELISA assays for clinical routine.