Blood-based biomarkers for Alzheimer’s disease: Current state and future use in a transformed global healthcare landscape

Neuron, Journal Year: 2023, Volume and Issue: 111(18), P. 2781 - 2799

Published: June 8, 2023

Language: Английский

---

Neurofilaments as biomarkers in neurological disorders — towards clinical application

Nature Reviews Neurology, Journal Year: 2024, Volume and Issue: 20(5), P. 269 - 287

Published: April 12, 2024

Language: Английский

---

The multifaceted role of neurofilament light chain protein in non-primary neurological diseases

Brain, Journal Year: 2022, Volume and Issue: 146(2), P. 421 - 437

Published: Sept. 8, 2022

The advancing validation and exploitation of CSF blood neurofilament light chain protein as a biomarker neuroaxonal damage has deeply changed the current diagnostic prognostic approach to neurological diseases. Further, recent studies have provided evidence potential new applications this also in non-primary In present review we summarize state art, future perspectives, but limitations, several medical fields, including intensive care medicine, surgery, internal medicine psychiatry. particular, is associated with degree impairment outcome patients admitted units or perioperative phase it seems be highly interconnected cardiovascular risk factors. Beyond that, interesting insights been by investigation psychiatric disorders well coronavirus disease-19 pandemic normal ageing. Altogether, data outline multifaceted applicability ranging from critical clinical setting development precision models suggesting strict interplay between nervous system pathophysiology health-illness continuum.

Language: Английский

---

The potential of blood neurofilament light as a marker of neurodegeneration for Alzheimer's disease

Brain, Journal Year: 2023, Volume and Issue: 147(1), P. 12 - 25

Published: Aug. 2, 2023

Over the past several years, there has been a surge in blood biomarker studies examining value of plasma or serum neurofilament light (NfL) as neurodegeneration for Alzheimer's disease. However, have limited efforts to combine existing findings assess utility NfL In addition, we still need better insight into specific aspects that are reflected by elevated concentration NfL. this review, survey literature on cross-sectional and longitudinal relationships between blood-based levels other, neuroimaging-based, indices individuals continuum. Then, based classification established FDA-NIH Biomarker Working group, determine marker monitoring disease status (i.e. biomarker) predicting severity older adults with without cognitive decline prognostic risk/susceptibility biomarker). The current suggest exhibits great promise because an increased level appears reflect atrophy, hypometabolism white matter integrity, particularly brain regions typically affected Longitudinal evidence indicates can be useful not only progression patients but also susceptibility/risk likelihood abnormal alterations structure function cognitively unimpaired higher risk developing (e.g. those amyloid-β). There limitations research, discussed review. Nevertheless, extant strongly suggests serve valuable susceptibility disease-related clinical settings, well research settings.

Language: Английский

---

Dynamics and prognostic value of serum neurofilament light chain in Guillain-Barré syndrome

EBioMedicine, Journal Year: 2024, Volume and Issue: 102, P. 105072 - 105072

Published: March 22, 2024

BackgroundNeurofilament light chain (NfL) is a biomarker for axonal damage in several neurological disorders. We studied the longitudinal changes serum NfL patients with Guillain-Barré syndrome (GBS) relation to disease severity, electrophysiological subtype, treatment response, and prognosis.MethodsWe included GBS who participated double-blind, randomised, placebo-controlled trial that evaluated effects of second course intravenous immunoglobulin (IVIg) on clinical outcomes. Serum levels were measured before initiation at one, two, four, twelve weeks using Simoa HD-X Analyzer. dynamics analysed linear mixed-effects models. Logistic regression was employed determine associations outcome prognostic value after correcting known markers.FindingsNfL tested from 281 patients. associated severity subtype. Strong found between high two inability walk unaided four (OR = 1.74, 95% CI 1.27–2.45), 26 2.79, 1.72–4.90). Baseline had most significant ability walk, independent predictors outcome. The time regain significantly longer highest baseline (p 0.0048) week 2 < 0.0001). No differences observed received IVIg vs. placebo.InterpretationSerum are involvement, poor GBS. potentially represents monitor neuronal an intermediate endpoint evaluate treatment.FundingPrinses Beatrix Spierfonds W.OR19-24.

Language: Английский

---

Novel Nose-to-brain delivery of carbenoxolone via mucoadhesive solid lipid nanoparticles for Parkinson’s symptoms management: In vitro and in vivo evaluation in a rotenone-induced rat model

International Journal of Pharmaceutics, Journal Year: 2025, Volume and Issue: 670, P. 125197 - 125197

Published: Jan. 8, 2025

Language: Английский

---

Brain injury in COVID-19 is associated with dysregulated innate and adaptive immune responses

Brain, Journal Year: 2022, Volume and Issue: 145(11), P. 4097 - 4107

Published: Sept. 6, 2022

COVID-19 is associated with neurological complications including stroke, delirium and encephalitis. Furthermore, a post-viral syndrome dominated by neuropsychiatric symptoms common, seemingly unrelated to severity. The true frequency underlying mechanisms of injury are unknown, but exaggerated host inflammatory responses appear be key driver We investigated the dynamics of, relationship between, serum markers brain [neurofilament light (NfL), glial fibrillary acidic protein (GFAP) total tau] dysregulated response (autoantibody production cytokine profiles) in 175 patients admitted 45 influenza. During hospitalization, sera from demonstrated elevations NfL GFAP severity-dependent manner, evidence ongoing active at follow-up 4 months later. These biomarkers were pro-inflammatory cytokines presence autoantibodies large number different antigens. Autoantibodies commonly seen against lung surfactant proteins also such as myelin glycoprotein. Commensurate findings influenza cohort. A distinct process characterized elevation tau was follow-up, which appeared independent initial disease severity not immune unlike GFAP. results demonstrate that common consequence both influenza, therefore likely feature severe viral infection more broadly. occurs context dysregulation innate adaptive responses, no single pathogenic mechanism clearly responsible.

Language: Английский

---

Plasma biomarkers for diagnosis of Alzheimer's disease and prediction of cognitive decline in individuals with mild cognitive impairment

Frontiers in Neurology, Journal Year: 2023, Volume and Issue: 14

Published: March 2, 2023

Background The last few years have seen major advances in blood biomarkers for Alzheimer's Disease (AD) with the development of ultrasensitive immunoassays, promising to transform how we diagnose, prognose, and track progression neurodegenerative dementias. Methods We evaluated a panel four novel electrochemiluminescence (ECL) immunoassays against presumed CNS derived proteins interest AD plasma [phosphorylated-Tau181 (pTau181), total Tau (tTau), neurofilament light (NfL), glial fibrillary acidic protein (GFAP)]. Two sets banked samples from Massachusetts Research Center's longitudinal cohort study were examined: A prognostic sample ( n = 85) consisting individuals mild cognitive impairment (MCI) 4 follow-up cross-sectional 238) AD, other diseases (OND), normal cognition (CN). Results Participants MCI who progressed dementia due probable during had higher baseline concentrations pTau181, NfL, GFAP compared non-progressors. best discrimination was observed pTau181 (AUC 0.83, 1.7-fold increase) 1.6-fold increase). autopsy- and/or biomarker verified levels tTau CN OND, while NfL elevated further increased OND. diagnostic (AD vs CN: AUC 0.90, 2-fold increase; vs. OND: 0.84, 1.5-fold but tTau, also showed good between 0.81–0.85; 1.5–2.2 fold Conclusions These new ECL assays demonstrated utility detection AD. Moreover, absolute reflect decline over next years, providing information that may both clinical practice trial populations.

Language: Английский

---

Neurofilament-Light, a Promising Biomarker: Analytical, Metrological and Clinical Challenges

International Journal of Molecular Sciences, Journal Year: 2023, Volume and Issue: 24(14), P. 11624 - 11624

Published: July 19, 2023

Neurofilament-light chain (Nf-L) is a non-specific early-stage biomarker widely studied in the context of neurodegenerative diseases (NDD) and traumatic brain injuries (TBI), which can be measured biofluids after axonal damage. Originally by enzyme-linked immunosorbent assay (ELISA) cerebrospinal fluid (CSF), Nf-L now quantified blood with emergence ultrasensitive assays. However, to ensure successful clinical implementation, reliable thresholds reference measurement procedures (RMP) should developed. This includes establishing distributing certified materials (CRM). As result complexity number circulating forms, clear definition what when immunoassays are used also critical achieving standardization long-term success those The use powerful tools such as mass spectrometry for developing RMP defining measurand ongoing. Here, we summarize current methods quantification biofluid showing potential implementation. progress challenges diagnostic tests addressed. Finally, discuss impact pathophysiological factors on levels establishment cut-off.

Language: Английский

---

Uman-type neurofilament light antibodies are effective reagents for the imaging of neurodegeneration

Brain Communications, Journal Year: 2023, Volume and Issue: 5(2)

Published: March 2, 2023

Abstract Recent work shows that certain antibody-based assays for the neurofilament light chain detect informative signals in CSF and blood of human animals affected by a variety CNS injury disease states. Much this has been performed using two mouse monoclonal antibodies to light, UD1 UD2, also known as Clones 2.1 47.3, respectively. These are essential components Uman Diagnostics Neurofilament-Light™ ELISA kit, Quanterix Simoa™ bead-based assay others. We show both bind neighbouring epitopes short, conserved unusual peptide centre Coil 2 segment ‘rod’ domain. describe surprising useful feature similar reagents. While other well-characterized generally robust staining countless cells processes sections from healthy rats, reveal only minor subset profiles, presumably spontaneously degenerating or degenerated neurons their processes. However, following experimental mid-cervical spinal cord injuries recognize numerous profiles fibre tracts damaged administered. were typically swollen, beaded, discontinuous sinusoidal expected found several C-terminal ‘tail’ region protein undamaged axonal but fail Uman-positive material. The unmasking loss tail can be mimicked treating with proteases suggesting immunostaining changes we discovered due neurodegeneration-induced proteolysis. have generated novel panel polyclonal directed against degeneration-specific properties identical Using these, which reagents contains further hidden distinct those recognized speculate Uman-type part binding important higher order assembly. provides insights into assay, describes tail-binding hypothesis relevant understanding

Language: Английский

---