Blood-based biomarkers for Alzheimer's disease: towards clinical implementation

The Lancet Neurology, Год журнала: 2021, Номер 21(1), С. 66 - 77

Опубликована: Ноя. 25, 2021

Язык: Английский

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Recent advances in the diagnosis and prognosis of amyotrophic lateral sclerosis

The Lancet Neurology, Год журнала: 2022, Номер 21(5), С. 480 - 493

Опубликована: Март 22, 2022

Язык: Английский

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Blood neurofilament light: a critical review of its application to neurologic disease

Annals of Clinical and Translational Neurology, Год журнала: 2020, Номер 7(12), С. 2508 - 2523

Опубликована: Ноя. 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.

Язык: Английский

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Alzheimer's disease: From immunotherapy to immunoprevention

Cell, Год журнала: 2023, Номер 186(20), С. 4260 - 4270

Опубликована: Сен. 1, 2023

Язык: Английский

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Axonal marker neurofilament light predicts long-term outcomes and progressive neurodegeneration after traumatic brain injury

Science Translational Medicine, Год журнала: 2021, Номер 13(613)

Опубликована: Сен. 29, 2021

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

Язык: Английский

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Neurofilaments as biomarkers in neurological disorders — towards clinical application

Nature Reviews Neurology, Год журнала: 2024, Номер 20(5), С. 269 - 287

Опубликована: Апрель 12, 2024

Язык: Английский

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Neurofilament Light Chain as Biomarker for Amyotrophic Lateral Sclerosis and Frontotemporal Dementia

Frontiers in Neuroscience, Год журнала: 2021, Номер 15

Опубликована: Июнь 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.

Язык: Английский

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

Brain, Год журнала: 2022, Номер 146(2), С. 421 - 437

Опубликована: Сен. 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.

Язык: Английский

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Plasma neurofilament light chain as a biomarker of Alzheimer’s disease in Subjective Cognitive Decline and Mild Cognitive Impairment

Journal of Neurology, Год журнала: 2022, Номер 269(8), С. 4270 - 4280

Опубликована: Март 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

Язык: Английский

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Novel App knock-in mouse model shows key features of amyloid pathology and reveals profound metabolic dysregulation of microglia

Molecular Neurodegeneration, Год журнала: 2022, Номер 17(1)

Опубликована: Июнь 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.

Язык: Английский

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