Biomarkers and Their Role in Neurodegenerative Diseases

Biomarkers are specific characteristics that can be used to predict the risk of disease, identify the presence of a disorder, and even pinpoint healthy biological processes. Oftentimes biomarkers are molecules found in bodily fluids such as blood or other tissues, and can be either single or a panel of multiple molecules.

Additionally, biomarkers can also be utilized to monitor whether a patient is responding to a course of treatment. This makes them critically important in therapeutic development, as they can indicate the efficacy of a treatment. Status as a biomarker is regulated, and qualifying a biomarker for use in detection of disease requires approval by the FDA.

Biomarkers have been used extensively for diseases such as cancer. In comparison, they have been less utilized for neurodegenerative diseases as fewer have been identified. The need for accurate, reliable, and easily accessible biomarkers is driven by the necessity of prompt diagnosis. Quick diagnosis of neurodegenerative diseases allows for improved patient treatment and symptom management, which are both critical to quality of life and prognosis.

There is currently a limited number of biomarkers approved for clinical diagnosis of neurodegenerative diseases. Three ligands have been approved in multiple countries as biomarkers for identification of Alzheimer’s disease. These ligands bind to amyloid-β, the protein that accumulates in the brains of Alzheimer’s patients. Using positron emission tomography (PET) scans of the brain, the ligands can be introduced via intravenous injection and then identified when bound to amyloid-β, indicating plaque presence and disease pathology.

Flortaucipir is a well-studied and FDA-approved biomarker for Alzheimer’s diagnosis. Flortaucipir binds to tau, another protein that accumulates in the brain of Alzheimer’s patients (however, it does not bind to tau in other neuropathologies). After intravenous injection, flortaucipir levels can be detected using PET scans of the brain, indicating tau aggregate presence with even greater specificity than is available with amyloid-β PET. Additionally, tau PET differentiates between Alzheimer’s and other neurodegenerative diseases with greater accuracy than MRI, making flortaucipir and similar biomarkers an invaluable tool for Alzheimer’s diagnosis.

. In recent years a new promising biomarker, Neurofilament light chain (NfL), has emerged that could identify the presence of neurodegenerative diseases. NfL is a protein normally located in the axons of neurons. During disease, cell death in the brain results in the release of NfL, which enters bodily fluids such as blood and cerebrospinal fluid. It can be easily detected with a blood draw (including plasma samples) or in cerebrospinal fluid via lumbar puncture (spinal tap). NfL detection could be indicative of neuron death, potentially caused by neurological disorders.

NfL has potential for use as a biomarker for Parkinson’s disease, Alzheimer’s, and Multiple Sclerosis, Amyotrophic Lateral Sclerosis, and traumatic brain injury such as concussion. Additionally, it is a possible biomarker for neuropathic Hunter Syndrome and stroke, and has been researched for its presence in the plasma of Creutzfeldt-Jakob disease patients. In Parkinson’s patients, NfL in the blood is consistently associated with motor and cognitive decline, and detection of NfL in cerebrospinal fluid during the early stages of Parkinson’s disease has been linked to reduced motor function and a decreased prognosis.NfL has the potential to significantly impact both the research and clinical fields. Because of this usefulness and accessibility, NfL is regarded as one of the most promising new biomarkers for the future of neurodegenerative study and treatment.