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Serum Neurofilament Light Chain Is a Potential Prognostic Biomarker for Frontotemporal Lobar Degeneration

By LabMedica International staff writers
Posted on 24 Jun 2020
A recent study has confirmed previous results showing that the protein serum neurofilament light chain is a potential prognostic biomarker for frontotemporal lobar degeneration.

The frontotemporal dementias (FTD) encompass six types of dementia involving the frontal or temporal lobes. They are: behavioral variant of FTD, semantic variant primary progressive aphasia, nonfluent agrammatic variant primary progressive aphasia, corticobasal syndrome, progressive supranuclear palsy, and FTD associated with motor neuron disease. Second only to Alzheimer's disease (AD) in prevalence, FTD accounts for 20% of young-onset dementia cases. Signs and symptoms typically manifest in late adulthood, more commonly between the ages of 45 and 65, approximately equally affecting men and women. Common signs and symptoms include significant changes in social and personal behavior, apathy, blunting of emotions, and deficits in both expressive and receptive language. Currently, there is no cure for FTD, but there are treatments that help alleviate symptoms. Due to the significant clinical overlap between FTLD spectrum disorders and late-onset primary psychiatric disorders (PPD), diagnostic biomarkers reflecting the different underlying pathophysiologies are urgently needed.

Seeking relevant diagnostic biomarkers, investigators at the University of Eastern Finland (Kuopio, Finland) compared the levels of serum neurofilament light chain (sNfL) in frontotemporal lobar degeneration (FTLD) patients of different clinical subtypes (bvFTD, PPA, and FTLD‐MND) and with or without the C9orf72 repeat expansion, and correlated sNfL levels with disease progression, assessed by the brain atrophy rate and survival time.

Neurofilament light chain is a neurofilament protein that in humans is encoded by the NEFL gene. Neurofilament light chain is a biomarker that can be measured with immunoassays in cerebrospinal fluid and plasma 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 C9orf72 gene is located on the short (p) arm of chromosome 9 at position 21.2. The mutation of C9ORF72 is a hexanucleotide repeat expansion of the six letter string of nucleotides GGGGCC. In a person without the mutation, there are few repeats of this hexanucleotide, typically less than 20-30, but in people with the mutation, the repeat can occur in the order of hundreds.

In this study, sNfL levels were determined from 78 FTLD patients (26 with C9orf72 repeat expansion and 52 lacking the repeat expansion) using the highly sensitive Quanterix (Billerica, MA, USA) Single Molecule Array (Simoa) NF-Light Advantage Kit. The Simoa method can detect considerably lower levels of protein biomarkers than other analytical methods. The progression of brain atrophy was evaluated using repeated T1‐weighted MRI scans and the survival time from medical records.

Results revealed that in the total FTLD cohort, sNfL levels were significantly higher in C9orf72 repeat expansion carriers compared to non‐carriers. Considering clinical phenotypes, sNfL levels were higher in the C9orf72 repeat expansion carriers than in the non‐carriers in bvFTD and PPA groups. Furthermore, sNfL levels were the highest in the FTLD‐MND group and the lowest in the bvFTD group. Higher sNfL levels significantly correlated with frontal cortical atrophy rate and subcortical grey matter atrophy rate. The higher sNfL levels also associated with shorter survival time.

The investigators concluded that, “Our results indicate that the C9orf72 repeat expansion carriers show elevated sNFL levels compared to non‐carriers and that the levels differ among different clinical phenotypes of FTLD. Higher sNfL levels correlated with a shorter survival time and cortical and subcortical atrophy rates. Thus, sNfL could prove as a potential prognostic biomarker in FTLD.”

The study was published in the May 22, 2020, online edition of the journal Annals of Clinical and Translational Neurology.

Related Links:
University of Eastern Finland
Quanterix



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