Current State and Future Directions in the Diagnosis of Amyotrophic Lateral Sclerosis DOI Creative Commons
Maximilian Vidovic, Lars Hendrik Müschen, Svenja Brakemeier

et al.

Cells, Journal Year: 2023, Volume and Issue: 12(5), P. 736 - 736

Published: Feb. 24, 2023

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease characterized by loss of upper and lower motor neurons, resulting in progressive weakness all voluntary muscles eventual respiratory failure. Non-motor symptoms, such as cognitive behavioral changes, frequently occur over the course disease. Considering its poor prognosis with median survival time 2 to 4 years limited causal treatment options, an early diagnosis ALS plays essential role. In past, has primarily been determined clinical findings supported electrophysiological laboratory measurements. To increase diagnostic accuracy, reduce delay, optimize stratification trials provide quantitative monitoring progression responsivity, research on disease-specific feasible fluid biomarkers, neurofilaments, intensely pursued. Advances imaging techniques have additionally yielded benefits. Growing perception greater availability genetic testing facilitate identification pathogenic ALS-related gene mutations, predictive access novel therapeutic agents addressing disease-modified therapies before advent first symptoms. Lately, personalized prediction models proposed offer more detailed disclosure for patient. this review, established procedures future directions diagnostics are summarized serve practical guideline improve pathway burdensome

Language: Английский

Blood-based biomarkers for Alzheimer's disease: towards clinical implementation DOI
Charlotte E. Teunissen, Inge M.W. Verberk, Elisabeth H. Thijssen

et al.

The Lancet Neurology, Journal Year: 2021, Volume and Issue: 21(1), P. 66 - 77

Published: Nov. 25, 2021

Language: Английский

Citations

356
Recent advances in the diagnosis and prognosis of amyotrophic lateral sclerosis DOI
Stephen A. Goutman, Orla Hardiman, Ammar Al‐Chalabi

et al.

The Lancet Neurology, Journal Year: 2022, Volume and Issue: 21(5), P. 480 - 493

Published: March 22, 2022

Language: Английский

Citations

285
Blood neurofilament light: a critical review of its application to neurologic disease DOI Creative Commons
Christian Barro, Tanuja Chitnis, Howard L. Weiner

et al.

Annals of Clinical and Translational Neurology, Journal Year: 2020, Volume and Issue: 7(12), P. 2508 - 2523

Published: Nov. 4, 2020

Abstract Neuronal injury is a universal event that occurs in disease processes affect both the central and peripheral nervous systems. A blood biomarker linked to neuronal would provide critical measure understand treat neurologic diseases. Neurofilament light chain (NfL), cytoskeletal protein expressed only neurons, has emerged as such biomarker. With ability quantify damage blood, NfL being applied wide range of conditions investigate monitor including assessment treatment efficacy. Blood not specific for one its release can also be induced by physiological processes. Longitudinal studies multiple sclerosis, traumatic brain injury, stroke show accumulation over days followed elevated levels months. Therefore, it may hard determine with single measurement when peak reached are normalized. Nonetheless, provides new diseases overcoming invasiveness CSF sampling restricted clinical application. In this review, we examine use biologic test disease.

Language: Английский

Citations

198
Alzheimer's disease: From immunotherapy to immunoprevention DOI Creative Commons
Mathias Jucker, Lary C. Walker

Cell, Journal Year: 2023, Volume and Issue: 186(20), P. 4260 - 4270

Published: Sept. 1, 2023

Language: Английский

Citations

132
Axonal marker neurofilament light predicts long-term outcomes and progressive neurodegeneration after traumatic brain injury DOI
Neil Graham, Karl Zimmerman, Federico Moro

et al.

Science Translational Medicine, Journal Year: 2021, Volume and Issue: 13(613)

Published: Sept. 29, 2021

Axonal injury after TBI can be reliably quantified using plasma NfL, which predicts long-term functional outcomes and progressive neurodegeneration.

Language: Английский

Citations

126
Neurofilaments as biomarkers in neurological disorders — towards clinical application DOI
Michael Khalil, Charlotte E. Teunissen, Sylvain Lehmann

et al.

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

Published: April 12, 2024

Language: Английский

Citations

111
Neurofilament Light Chain as Biomarker for Amyotrophic Lateral Sclerosis and Frontotemporal Dementia DOI Creative Commons
Federico Verde, Markus Otto, Vincenzo Silani

et al.

Frontiers in Neuroscience, Journal Year: 2021, Volume and Issue: 15

Published: June 21, 2021

Amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) are two related currently incurable neurodegenerative diseases. ALS is characterized by degeneration of upper lower motor neurons causing relentless paralysis voluntary muscles, whereas in FTD, progressive atrophy the frontal temporal lobes brain results deterioration cognitive functions, language, personality, behavior. In contrast to Alzheimer’s disease (AD), FTD still lack a specific neurochemical biomarker reflecting neuropathology ex vivo . However, past 10 years, considerable progress has been made characterization neurofilament light chain (NFL) as cerebrospinal fluid (CSF) blood for both NFL structural component axonal cytoskeleton released into CSF consequence damage or degeneration, thus behaving general relatively non-specific marker neuroaxonal pathology. ALS, elevation its levels exceeds that observed most other neurological diseases, making it useful discrimination from mimic conditions potentially worthy consideration introduction diagnostic criteria. Moreover, correlates with progression rate negatively associated survival, providing prognostic information. patients, elevated compared healthy individuals and, lesser extent, patients forms dementia, but latter difference not sufficient enable satisfying performance at individual patient level. also several measures severity. Due technological progress, can now be quantified peripheral blood, where present much concentrations CSF, allowing less invasive sampling, scalability, longitudinal measurements. The promoted innovative studies demonstrating kinetics presymptomatic harboring gene mutations FTD. Especially generally stable over time, which, together their correlation rate, makes an ideal pharmacodynamic therapeutic trials. this review, we illustrate significance discuss unsolved issues potential future developments.

Language: Английский

Citations

104
The multifaceted role of neurofilament light chain protein in non-primary neurological diseases DOI Open Access
Samir Abu‐Rumeileh, Ahmed Abdelhak, Matteo Foschi

et al.

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

Citations

82
Plasma neurofilament light chain as a biomarker of Alzheimer’s disease in Subjective Cognitive Decline and Mild Cognitive Impairment DOI Creative Commons
Giulia Giacomucci, Salvatore Mazzeo, Silvia Bagnoli

et al.

Journal of Neurology, Journal Year: 2022, Volume and Issue: 269(8), P. 4270 - 4280

Published: March 14, 2022

Abstract Introduction Neurofilament light chain (NfL) is becoming increasingly notable in neurological diseases including AD, and it has been suggested as a new peripherical biomarker of neurodegeneration. We aimed to compare plasma NfL levels among Subjective Cognitive Decline (SCD), Mild Impairment (MCI), AD patients evaluate relationships between CSF biomarkers neuropsychological scores. Materials methods enrolled 110 (34 SCD, 53 MCI, 23 AD), who underwent clinical evaluation, APOE genotyping, analysis. Ninety-one at least one amyloid burden (CSF and/or PET); 86 also phosphorylated-tau (p-tau) total-tau (t-tau) measurement. Patients were classified A + if they presented positive or A− not. Results significantly increased MCI compared SCD patients. These differences depend on status, e.g., had lower NfLs than but comparable with A−. Similarly, higher A−, AD. correlated p-tau all No correlations found subgroup. In negatively memory test Conclusions Plasma might be promising for neurodegeneration discriminate cognitive decline due from other conditions causing impairment prodromal stages. Considering tests useful peripheral preclinical phases

Language: Английский

Citations

73
Novel App knock-in mouse model shows key features of amyloid pathology and reveals profound metabolic dysregulation of microglia DOI Creative Commons
Dan Xia, Steve Lianoglou, Thomas Sandmann

et al.

Molecular Neurodegeneration, Journal Year: 2022, Volume and Issue: 17(1)

Published: June 11, 2022

Genetic mutations underlying familial Alzheimer's disease (AD) were identified decades ago, but the field is still in search of transformative therapies for patients. While mouse models based on overexpression mutated transgenes have yielded key insights mechanisms disease, those are subject to artifacts, including random genetic integration transgene, ectopic expression and non-physiological protein levels. The engineering novel using knock-in approaches addresses some limitations. With mounting evidence role played by microglia AD, high-dimensional phenotype critical refine our understanding immune response brain.We engineered a App model (AppSAA) homologous recombination introduce three disease-causing coding (Swedish, Arctic Austrian) gene. Amyloid-β pathology, neurodegeneration, glial responses, brain metabolism behavioral phenotypes characterized heterozygous homozygous AppSAA mice at different ages and/ or biofluids. Wild type littermate used as experimental controls. We situ imaging technologies define whole-brain distribution amyloid plaques compare it other AD human pathology. To further explore microglial relevant we isolated with fibrillar Aβ content from performed transcriptomics metabolomics analyses vivo measure energy response. Finally, also various assays.Leveraging multi-omics approaches, discovered profound alteration diverse lipids metabolites well an exacerbated disease-associated transcriptomic high intracellular content. recapitulates pathological features such progressive accumulation parenchymal vascular deposits, altered astroglial responses elevation CSF markers neurodegeneration. Those observations associated increased TSPO FDG-PET signals hyperactivity animals aged.Our findings demonstrate that lipid dyshomeostasis consistent lysosomal dysfunction foam cell immuno-metabolic perturbations, opening new avenues investigate metabolic pathways play responding AD-relevant pathogenesis. in-depth characterization hallmarks this open-access should serve resource scientific community disease-relevant biology.

Language: Английский

Citations

73