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A single blood-based biomarker helps indicate underlying neurodegeneration

 


The level of a protein called neurofilament light chain (NfL) in the blood allows for neurodegenerative diseases such as Down’s dementia, motor neuron disease (ALS), and frontotemporal dementia, even if the clinical symptoms are uncertain. You can identify people who have sex.

Was announced in Nature Communications Funded by the NIHR Maudsley Biomedical Research Center, this study determines a set of age-related NfL cutoff levels that can signal potential use in a primary care environment with a simple blood test. Did.

The co-lead authors of this study, Dr. Abdul Hay of the NIHR Moseley Biomedical Research Center and Moseley NHS Foundation Trust in King’s College London and South London, said: Existence of underlying neurodegeneration with excellent accuracy. This is not limited to specific disorders, but may be useful for services such as memory clinics as a rapid screening tool to determine if memory, thinking, or mental disorders are the result of neurodegeneration. ..

Neurodegenerative disease is a debilitating condition that results in ongoing degeneration or death of nerve cells, causing problems with thinking, attention, and memory. Currently, there are approximately 850,000 people with dementia in the UK, which is projected to grow to 1.6 million by 2040. The development of dementia is being promoted to identify the onset of these debilitating diseases and take preventive measures as soon as possible. A reliable and accessible biomarker that can recognize or eliminate processes in the brain that cause neurodegeneration.

Current biomarkers used to identify neurodegenerative diseases are taken from the body fluid (cerebrospinal fluid-CSF) that surrounds the brain and spinal column and must be extracted using an invasive technique called lumbar puncture. Advances have been made to use biomarkers from blood that provide a more accessible and comfortable assessment. A central and irreversible feature of many neurodegenerative diseases is damage to nerve fibers, resulting in the release of neurofilament light chains (NfL).

Using ultrasensitive tests, NfL can be detected at low levels in the blood and is increased in many diseases, unlike phosphorylated tau, which is specific to Alzheimer’s disease. This means that the NfL can be used in many neurodegenerative disease diagnostic processes. In particular, this study includes Down’s syndrome, ALS, and frontotemporal dementia.

Professor Ammar Al-Chalabi, co-author of King’s College London, and co-leader of NIHR Maudsley BRC’s research themes in psychosis and neuropsychiatry. In neurodegenerative diseases such as Alzheimer’s disease, Parkinson’s disease, and motor neuron disease, blood tests that enable early diagnosis and help monitor disease progression and response to treatment are very helpful. Neurofilament light chains are promising biomarkers that can speed up the diagnosis of neurodegenerative diseases and shorten clinical trials.

This study examined 3138 samples from King’s College London, Lund University, and the Alzheimer’s Disease Neuroimaging Initiative, including people without cognitive impairment, people with neurodegenerative disorders, people with Down syndrome, and people with depression. This study showed that blood NfL levels were higher in all neurodegenerative disorders and highest in patients with Down’s disease, motor neuron disease, and frontotemporal dementia compared to patients without cognitive impairment. I did.

The study also showed that blood-based NfL cannot distinguish between all disorders, but can provide insights into different groups within a particular disorder. For example, in patients with Parkinson’s disease, high levels of NfL showed atypical Parkinson’s disease, and in patients with Down’s disease, NfL levels were different between patients with dementia and those without dementia.

Co-author Andre Stridham, a professor of intellectual disability at King’s College London, said, “This study found that light chain levels in neurofilaments increased especially in Down’s syndrome adults with a genetic predisposition to Alzheimer’s disease. In addition, those who were diagnosed with dementia after the onset of Alzheimer’s disease had higher levels than those who did not.

This means that this new marker may be used to improve the diagnosis of Alzheimer’s disease in people with Down syndrome and as a biomarker to indicate whether treatment is effective. Suggests. It’s a great pleasure for people with Down Syndrome to have only a simple blood test and tolerate it more than a brain scan.

This study evaluated age-related thresholds or cutoffs for NfL concentrations that could represent the time when an individual was diagnosed. These age-related cutoff points were 90% accurate in highlighting neurodegeneration over the age of 65 and 100% accurate in detecting motor neuron disease and Down’s syndrome dementia in King’s College London samples. .. sample. Importantly, the NfL can distinguish individuals with depression from those with neurodegenerative disorders who commonly present with primary psychiatric disorders in the early stages of developing diseases such as frontotemporal dementia. It’s done.

“Blood tests have great potential to improve the diagnosis of dementia in both specialized memory clinics and primary care,” said Professor Oscar Hanson, co-chief author at Lund University. As shown in large studies, it is very useful in many clinical scenarios that can provide a great deal of information to doctors.

“Blood-based NfLs provide a scalable and widely available alternative to invasive and expensive tests for dementia,” said Dr. Hye. This is in some European countries, such as Sweden and the Netherlands. Used as a routine assessment in the Netherlands, age-related cutoffs provide clinicians with benchmarks and quickly accessible tests to show neurodegeneration in people with thought and memory problems. I can do it. .’

An exciting time when we begin to provide meaningful, non-invasive insights into brain damage by combining blood tests such as plasma NfL with other new blood biomarkers such as phosphorylated tau (p-tau). Is rushing into.

Dr. Nicholas Ashton, Principal Investigator, King’s College London

Source:

Journal reference:

Ashton, NJ, Et al.(2021) Multicenter verification research on the diagnostic value of plasma neurofilament lights. Nature Communications.. doi.org/10.1038/s41467-021-23620-z..

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