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Neurofilament Light Chain Levels Increase Accuracy of Neurodegenerative Disease Detection

By LabMedica International staff writers
Posted on 27 Jul 2021
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Image: Neuropathologic analysis of brain tissue from FTLD patients. Ubiquitin immunohistochemistry in cases of familial FTLD demonstrates staining of (a) neurites and neuronal cytoplasmic inclusions in the superficial cerebral neocortex, (b) neuronal cytoplasmic inclusions in hippocampal dentate granule cells, and (c) neuronal intranuclear inclusions in the cerebral neocortex (arrows) (Photo courtesy of Wikimedia Commons)
Image: Neuropathologic analysis of brain tissue from FTLD patients. Ubiquitin immunohistochemistry in cases of familial FTLD demonstrates staining of (a) neurites and neuronal cytoplasmic inclusions in the superficial cerebral neocortex, (b) neuronal cytoplasmic inclusions in hippocampal dentate granule cells, and (c) neuronal intranuclear inclusions in the cerebral neocortex (arrows) (Photo courtesy of Wikimedia Commons)
Increased accuracy in early detection of neurodegenerative diseases was obtained by adding determination of levels of neurofilament light chain (NfL) protein in cerebrospinal fluid (CSF) to the framework that combines three Alzheimer's disease biomarkers - pathologic amyloid plaques (A), tangles (T), and neurodegeneration (N), collectively called ATN.

Neurofilament light chain, is a neurofilament protein that in humans is encoded by the NEFL gene. It is a biomarker that can be measured in samples of cerebrospinal fluid or plasma with immunoassays and reflects axonal damage in a wide variety of neurological disorders. It is a useful marker for disease monitoring in amyotrophic lateral sclerosis, multiple sclerosis, Alzheimer's disease, and more recently Huntington's disease.

The ATN framework provides an in vivo diagnosis of Alzheimer's disease (AD) using CSF biomarkers. However, ATN is rarely evaluated in pathologically confirmed patients and its poor sensitivity to suspected non-Alzheimer's syndromes, including frontotemporal lobar degeneration (FTLD), leads to misdiagnoses.

In this light, investigators at the University of Pennsylvania School of Medicine (Philadelphia, USA) compared accuracy of ATN using CSF total tau (ATNTAU) to a modified strategy using CSF neurofilament light chain (ATNNfL) in an autopsy cohort.

Results revealed that ATNNfL more accurately identified FTLD than ATNTAU, even in cases with co-occurring AD and FTLD. ATNNfL misclassified fewer AD and FTLD as "normal" (2%) than ATNTAU (14%).

"CSF biomarkers work similarly to a pregnancy test, offering a simple positive or negative result when enough of a substance is detected. But like a pregnancy test, biomarkers for Alzheimer's disease can provide false negatives or positives," said first author Dr. Katheryn A.Q. Cousins, research associate in neurology at the University of Pennsylvania School of Medicine. "Alzheimer's is a diverse disease, and it is common for other conditions to also be present in the brain. The ATN framework may provide a more complete look at a person's diagnosis and give us a much richer understanding of not only Alzheimer's disease, but other co-occurring neurodegenerative conditions. However, to accomplish this, additional biomarkers that can detect other neurodegenerative conditions are critically needed."

"While the ATN framework is very exciting and offers much opportunity for patients with Alzheimer's disease, these biomarkers do not capture every case of the disease. We want to be able to detect and treat every patient with neurodegenerative disease as early as possible, and more research is needed to fully understand how biofluids track with the disease process," said Dr. Cousins. "I am eager to conduct additional research into which patients might be missed by these markers, what they have in common, and what causes the pathological and clinical differences in the disease."

The study demonstrating the advantage of adding neurofilament light protein to the ATN framework was published in the May 2021 issue of the journal Alzheimer's and Dementia: The Journal of the Alzheimer's Association.

Related Links:
University of Pennsylvania School of Medicine

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