A majority of current disease-modifying therapeutic approaches for age-related neurodegenerative diseases target their characteristic proteopathic lesions (α-synuclein, Tau, Aβ). To monitor such treatments, fluid biomarkers reflecting the underlying disease process are crucial. We found robust increases of neurofilament light chain (NfL) in CSF and blood in murine models of α-synucleinopathies, tauopathy, and β-amyloidosis. Blood and CSF NfL levels were strongly correlated, and NfL increases coincided with the onset and progression of the corresponding proteopathic lesions in brain. Experimental induction of α-synuclein lesions increased CSF and blood NfL levels, while blocking Aβ lesions attenuated the NfL increase. Consistently, we also found NfL increases in CSF and blood of human α-synucleinopathies, tauopathies, and Alzheimer's disease. Our results suggest that CSF and particularly blood NfL can serve as a reliable and easily accessible biomarker to monitor disease progression and treatment response in mouse models and potentially in human proteopathic neurodegenerative diseases.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1016/j.neuron.2016.05.018 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
INTERCEPT-AD, a phase 1 study of intravenous sabirnetug in participants with mild cognitive impairment or mild dementia due to Alzheimer's disease.
J Prev Alzheimers Dis
January 2025
CenExel iResearch, Atlanta, GA, USA.
Background: Soluble species of multimeric amyloid-beta including globular amyloid-beta oligomers (AβOs) and linear amyloid-beta protofibrils are toxic to neurons. Sabirnetug (ACU193) is a humanized monoclonal antibody, raised against globular species of soluble AβO, that has over 650-fold greater binding affinity for AβOs over monomers and appears to have relatively little binding to amyloid plaque.
Objectives: To assess safety, pharmacokinetics, and exploratory measures including target engagement, biomarker effects, and clinical efficacy of sabirnetug in participants with early symptomatic Alzheimer's disease (AD; defined as mild cognitive impairment and mild dementia due to AD).
Peripheral neurofilament light chain and intracortical myelin in bipolar I disorder.
J Affect Disord
January 2025
Centre for Clinical Neurosciences, McMaster University, Canada; Department of Psychiatry and Behavioural Neurosciences, McMaster University, Hamilton, ON, Canada; Mood Disorders Treatment and Research Centre and Women's Health Concerns Clinic, St. Joseph's Healthcare Hamilton, ON, Canada. Electronic address:
Background: Neurofilament light chain (NfL) is a cytoskeletal protein that supports neuronal structure. Blood NfL levels are reported to be higher in diseases where myelin is damaged. Studies investigating intracortical myelin (ICM) in bipolar disorder (BD) have reported deficits in ICM maturation over age.
View Article and Find Full Text PDFAmyotrophic lateral sclerosis in a patient with chronic lymphocytic leukaemia and drug related sarcoid-like reaction.
BMC Neurol
January 2025
Department of Neurology, Wessex Neurological Centre, University Hospital Southampton, Southampton, UK.
Article Synopsis
- Sarcoid-like reaction (SLR) is an immune response affecting lymph nodes and organs, which doesn't fulfill the criteria for systemic sarcoidosis, and can be associated with certain diseases like Chronic lymphocytic leukaemia (CLL) and Amyotrophic lateral sclerosis (ALS).
- A 60-year-old male patient with treated CLL developed ALS symptoms following exposure to Venetoclax and Rituximab, presenting with rashes and weakness that progressed over a year.
- Diagnosis complications included atypical signs and symptoms, leading to misdiagnosis of neurosarcoidosis and challenges in treatment, despite initial interventions with prednisolone and infliximab.
The Role of GFAP in Post-Mortem Analysis of Traumatic Brain Injury: A Systematic Review.
Int J Mol Sci
December 2024
Institute of Legal Medicine, Department of Medical and Surgical Sciences, Magna Graecia University, 88100 Catanzaro, Italy.
Traumatic brain injuries (TBIs) are a leading cause of mortality and morbidity, particularly in forensic settings where determining the cause of death and timing of injury is critical. Glial fibrillary acidic protein (GFAP), a biomarker specific to astrocytes, has emerged as a valuable tool in post-mortem analyses of TBI. A PRISMA-based literature search included studies examining GFAP in human post-mortem samples such as brain tissue, cerebrospinal fluid (CSF), serum, and urine.
View Article and Find Full Text PDFNeurofilament Light Protein as a Biomarker in Severe Mental Disorders: A Systematic Review.
Int J Mol Sci
December 2024
Molecular Markers Laboratory, IRCCS Istituto Centro San Giovanni di Dio Fatebenefratelli, 25125 Brescia, Italy.
Severe mental disorders (SMDs), such as schizophrenia (SZ), bipolar disorder (BD), and major depressive disorder (MDD), are heterogeneous psychiatric diseases that impose a significant societal burden due to their chronic disabling nature. There are no objective and reliable diagnostic tests for SMDs; thus, there is an urgent need for specific biomarkers to improve diagnosis, treatment, and resource allocation. Neurofilaments, found in cerebrospinal fluid and blood, offer reliable diagnostic and prognostic potential.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!