| Michael Khalil, Charlotte E. Teunissen, Markus Otto, Frederik Piehl, Maria Pia Sormani, Thomas Gatteringer, Christian Barro, Ludwig Kappos, Manuel Comabella, Franz Fazekas, Axel Petzold, Kaj Blennow, Henrik Zetterberg, Jens Kuhle
Neurofilaments are promising biomarkers for detecting neuroaxonal damage in neurological disorders. Their levels rise in cerebrospinal fluid (CSF) and blood upon axonal injury, making them useful for monitoring disease activity and treatment responses. First-generation assays were insufficiently sensitive, but third- and fourth-generation technologies, such as electrochemiluminescence and single molecule array (SiMoA), enable reliable detection of neurofilament levels in blood, even in mild disease and healthy individuals. These advancements allow longitudinal monitoring of disease progression and drug effects in clinical trials. Neurofilaments are abundant in neurons and reach pathological levels in various diseases, including neurodegenerative, inflammatory, and traumatic conditions. They are highly specific for neuronal damage and can indicate axonal injury regardless of the underlying pathology. Neurofilament light (NfL) levels in blood correlate with CSF levels, enabling non-invasive monitoring of neuroaxonal damage without lumbar puncture. NfL is a promising biomarker for multiple sclerosis, dementia, stroke, traumatic brain injury, amyotrophic lateral sclerosis, and Parkinson disease. Studies show that NfL levels in blood can predict disease progression and treatment response. In dementia, NfL levels are elevated in Alzheimer's, frontotemporal dementia, and Lewy body dementia, and correlate with brain atrophy and cognitive decline. In stroke, NfL levels in blood are higher in patients with ischaemic stroke compared to those with transient ischaemic attacks. In traumatic brain injury, NfL levels in blood increase after mild TBI and correlate with axonal injury. In ALS, NfL levels are elevated in CSF and blood, and correlate with disease progression. In Parkinson disease, NfL levels in CSF are increased in atypical parkinsonian syndromes compared to Parkinson's disease. NfL levels in blood are also elevated in Huntington disease and some subtypes of bipolar disorder. Neurofilament measurements have the potential to improve diagnosis, monitoring, and treatment of neurological disorders. Future studies are needed to validate NfL as a biomarker in clinical trials and to establish normal ranges across age groups. Standardized assays and longitudinal studies are essential for translating neurofilament measurements into clinical practice.Neurofilaments are promising biomarkers for detecting neuroaxonal damage in neurological disorders. Their levels rise in cerebrospinal fluid (CSF) and blood upon axonal injury, making them useful for monitoring disease activity and treatment responses. First-generation assays were insufficiently sensitive, but third- and fourth-generation technologies, such as electrochemiluminescence and single molecule array (SiMoA), enable reliable detection of neurofilament levels in blood, even in mild disease and healthy individuals. These advancements allow longitudinal monitoring of disease progression and drug effects in clinical trials. Neurofilaments are abundant in neurons and reach pathological levels in various diseases, including neurodegenerative, inflammatory, and traumatic conditions. They are highly specific for neuronal damage and can indicate axonal injury regardless of the underlying pathology. Neurofilament light (NfL) levels in blood correlate with CSF levels, enabling non-invasive monitoring of neuroaxonal damage without lumbar puncture. NfL is a promising biomarker for multiple sclerosis, dementia, stroke, traumatic brain injury, amyotrophic lateral sclerosis, and Parkinson disease. Studies show that NfL levels in blood can predict disease progression and treatment response. In dementia, NfL levels are elevated in Alzheimer's, frontotemporal dementia, and Lewy body dementia, and correlate with brain atrophy and cognitive decline. In stroke, NfL levels in blood are higher in patients with ischaemic stroke compared to those with transient ischaemic attacks. In traumatic brain injury, NfL levels in blood increase after mild TBI and correlate with axonal injury. In ALS, NfL levels are elevated in CSF and blood, and correlate with disease progression. In Parkinson disease, NfL levels in CSF are increased in atypical parkinsonian syndromes compared to Parkinson's disease. NfL levels in blood are also elevated in Huntington disease and some subtypes of bipolar disorder. Neurofilament measurements have the potential to improve diagnosis, monitoring, and treatment of neurological disorders. Future studies are needed to validate NfL as a biomarker in clinical trials and to establish normal ranges across age groups. Standardized assays and longitudinal studies are essential for translating neurofilament measurements into clinical practice.