Using Nfl To Fight Brain Injury And Neurodegenerative Diseases
By Dr. Andreas Jeromin, PH.D., Chief Medical Officer (Consulting), Quanterix
When we think of the letters N-F-L, our minds are drawn to football and the National Football League. However, NFL, or ineurofilament light chain as the non-abbreviated name, is also a powerful protein that has shown promise for the early detection and diagnosis of brain injuries, as well as several neurodegenerative diseases, such as Alzheimer’s and Parkinson’s disease.
Let’s first take a look at the applications of NFL for Alzheimer’s disease (AD). With varying symptoms that can often be disguised by patients, Alzheimer’s is a difficult disease to detect and has traditionally gone under-diagnosed, with the Alzheimer’s Association reporting that as many as half of all people with Alzheimer’s and other dementias have not been diagnosed. Currently, the analysis of biomarkers in cerebrospinal fluid (CSF) is used to aid in the diagnosis, however CSF can only be obtained by lumbar puncture, which is a painful and invasive procedure. Further, efforts to find reliable blood biomarkers for AD have previously proven difficult, due largely to a lack of sensitivity in current detection methodologies, which has impeded researchers’ ability to take accurate biomarker measurements.
A recent study, published in JAMA Neurology, showed a correlation between NfL and Alzheimer’s disease (AD) diagnoses. Using our ultra-sensitive Simoa technology, researchers measured plasma NfL concentration in 193 cognitively healthy controls, 197 patients with mild cognitive impairment (MCI), and 180 patients with AD dementia, and found that plasma NfL correlated with CSF NfL. It also showed that plasma NfL was increased in patients with MCI and patients with AD dementia compared with controls, and appears to have a prognostic rolew. NfL was also particularly high in patients with MCI and patients with AD dementia with Aβ pathologic features. These findings highlight the potential for using plasma NfL as a noninvasive biomarker for AD diagnoses, which is incredibly groundbreaking.
Parkinson’s disease (PD) is another disease that has long given researchers challenges. With no known cure, doctors have searched for a way to detect early signs of the disease to better slow its progression. Similar to Alzheimer’s however, while researcher have long been studying NfL proteins in CSF, the required lumbar puncture is not appealing to patients, due to its invasiveness and painfulness. Another recent study, published in Neurology, found that a sensitive test for NfL in blood can be used to distinguish between Parkinson disease (PD) and atypical parkinsonian disorders (APD) with unprecedented accuracy.
PD, which affects more than 10 million people worldwide, according to the Parkinson’s Disease Foundation, is the most common neurodegenerative cause of parkinsonism. However, there are several other causes, such as multiple system atrophy and progressive supranuclear palsy, commonly referred to as APDs. These diseases, unlike PD, do not respond well to dopaminergic treatments and often result in a far worse prognosis for patients. Discriminating between PD and APD based on clinical symptoms, has been a challenge for researchers and clinicians, but a vital step in determining effective treatment and positive patient outcomes. This study showed strong correlations between blood and CSF concentrations of NfL, offering support for the use of blood-based testing for the distinction of PD and APD.
Yet another study of NCAA Division 1 football players, done in conjunction with Texas Christian University, showed NfL to be a reliable biomarker for the diagnosis of concussions. Researchers used Simoa to identify differences in baseline NfL levels, between the football players and non-contact sport athletes. Published in the Journal of Neurotrauma, the study examined changes in NfL levels in players over the course of the season. It found that a season of collegiate football is associated with elevated levels of NfL, which is indicative of head injuries like concussions, thus pointing to a potential correlation between contact sports and concussions.
We are excited to have the opportunity to share these findings and other research around the potential of NfL, as well as several other biomarkers for the diagnosis of these and other neurological diseases, at the 13th International Conference on Alzheimer’s and Parkinson’s Diseases (AD/PD) this week. With a goal of unraveling the mechanisms and improving the treatment of Alzheimer’s, Parkinson’s and other related neurodegenerative diseases, the conference brings together the top medical and scientific professionals from around the world. Among the studies that we will be sharing at this event will be research on the development of a fully automated digital immunoassay for NfL for blood and CSF. We’ll demonstrate how the Simoa NfL assay reliably measures NfL in plasma, serum and CSF samples from healthy and diseased individuals and can facilitate the research and diagnostic development of NfL as a biomarker for neurodegeneration.
Additionally, we will also be showcasing the Simoa TDP-43 assay and the digital Simoa mouse Tau assay, which we developed to advance the understanding of neurodegenerative diseases. We’ll discuss the development of these assays and are part of the rapidly expanding toolbox of ultrasensitive Simoa assay, revolutionizing CNS biomarkers. To learn more about our neurology assays and hear about how our Simoa technology is accelerating research across this therapeutic area, come visit us at booth #36 at AD/PD or visit the neurology section of our website.
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