The presence of underlying neurodegeneration in people with cognitive issues can be identified by a single biomarker, research has revealed.
Researchers from King’s College London have discovered that levels of a protein called neurofilament light chain (NfL) in the blood can identify those who might have neurodegenerative diseases such as Down’s syndrome dementia, motor neuron disease (ALS), and frontotemporal dementia, when clinical symptoms are not definitive.
The study, which was part-funded by the NIHR Maudsley Biomedical Research Centre, has been published in Nature Communications.
Dr Abdul Hye, from the NIHR Maudsley Biomedical Research Centre at King’s College London and South London and Maudsley NHS Foundation Trust and joint senior author on the study, said: “For the first time, we have shown across a number of disorders that a single biomarker can indicate the presence of underlying neurodegeneration with excellent accuracy. Though it is not specific for any one disorder, it could help in services such as memory clinics as a rapid screening tool to identify whether memory, thinking, or psychiatric problems are a result of neurodegeneration.”
Neurodegenerative diseases result in ongoing degeneration or death of nerve cells, leading to problems in thought, attention, and memory. In order to help identify the onset of these debilitating diseases and put in place preventative measures as early as possible, there has been a drive to develop reliable and accessible biomarkers that can recognise or rule out whether the processes in the brain that are responsible for neurodegeneration are occurring.
Current biomarkers used to identify neurodegenerative disorders are taken from the fluid that surrounds the brain and spinal column (cerebrospinal fluid – CSF), which has to be extracted using an invasive procedure called lumbar puncture. Advances have been made to use biomarkers from the blood which would provide a more accessible and comfortable assessment. A central and irreversible feature in many neurodegenerative disorders is damage to the nerve fibre which results in the release of neurofilament light chain (NfL). Using ultrasensitive tests, NfL can be detected in blood at low levels and is increased in a number of disorders, unlike phosphorylated tau which is specific for Alzheimer’s disease. This means NfL can be of use in the diagnostic process of many neurodegenerative diseases most notably in this study Down’s syndrome dementia, ALS, and frontotemporal dementia.
Simple blood test
Co-author Professor Ammar Al-Chalabi from King’s College London and co-lead of the Psychosis and Neuropsychiatry research theme at the NIHR Maudsley BRC, said: “For neurodegenerative diseases like Alzheimer’s, Parkinson’s, or motor neuron disease, a blood test to allow early diagnosis and help us monitor disease progression and response to treatment would be very helpful. Neurofilament light chain is a promising biomarker that could speed diagnosis of neurodegenerative diseases and shorten clinical trials.”
The study examined 3138 samples from King’s College London, Lund University, and Alzheimer’s Disease Neuroimaging Initiative, including people with no cognitive impairment, people with neurodegenerative disorders, people with Down’s syndrome and people with depression. The study showed that concentrations of NfL in the blood were higher across all neurodegenerative disorders, compared to those with no cognitive problems, the highest being in people with dementia and Down’s syndrome, motor neuron disease, and frontotemporal dementia.
The study also showed that, although blood-based NfL could not differentiate between all the disorders, it could provide insight into different groups within certain disorders. For example, in those with Parkinson’s a high concentration of NfL indicated atypical Parkinson’s disorder and in patients with Down’s syndrome, NfL levels differentiated between those with and without dementia.
The study assessed age-related thresholds or cut-offs of NfL concentrations that could represent the point at which an individual would receive a diagnosis. These age-related cut-off points were 90% accurate in highlighting neurodegeneration in those over 65 years of age and 100% accurate in detecting motor neurone disease and Down’s syndrome dementia in the King’s College London samples, with a very similar result in the Lund samples. Importantly, NfL was able to distinguish individuals with depression from individuals with neurodegenerative disorders which commonly present with primary psychiatric disorder in the onset of disease development such as frontotemporal dementia.