Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2025 May;62(5):6273-6282.
doi: 10.1007/s12035-024-04671-x. Epub 2025 Jan 6.

Lower Circulating Gas6 Levels Are Associated with Bulbar Phenotype and Faster Disease Progression in Amyotrophic Lateral Sclerosis Patients

Daria Apostolo  1 , Luciana L Ferreira  1 , Davide D'Onghia  1 , Federica Vincenzi  1 , Nicole Vercellino  1 , Mattia Perazzi  1   2 , Mario Pirisi  1   2 , Roberto Cantello  1   2 , Rosalba Minisini  1 , Letizia Mazzini  1   2 , Mattia Bellan  3   4 , Fabiola De Marchi  1   2
Affiliations

Lower Circulating Gas6 Levels Are Associated with Bulbar Phenotype and Faster Disease Progression in Amyotrophic Lateral Sclerosis Patients

Daria Apostolo et al. Mol Neurobiol. 2025 May.

Abstract

Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disorder that primarily affects the motor neurons in the brain and spinal cord. While the exact cause of ALS is not fully understood, a combination of genetic and environmental factors is believed to contribute to its development. Growth arrest-specific 6 (Gas6), a vitamin K-dependent protein, has been recognized to enhance oligodendrocytes and neurons' survival and is associated with different kinds of (neuro)inflammatory conditions. Therefore, we aimed to determine a possible implication of Gas6 in ALS phenotype and progression by evaluating the value of circulating Gas6 and its soluble receptors (sAxl, sMer, sTyro-3) in ALS patients. We conducted a prospective observational study including 65 ALS patients and measured the circulating serum levels of Gas6, sAxl, sMer, soluble Tyro-3 (sTyro-3), and neurofilaments (NfLs). In our ALS cohort, lower serum levels of Gas6 and concomitantly higher levels of NfLs were associated with a more aggressive disease, expressed with bulbar phenotype (p-value for Gas6 = 0.03) and faster progression (p-value for Gas6 = 0.03). Also, serum Gas6 was able to distinguish (area under the curve, cut-off 13.70 ng/mL, sensitivity 69.57%, specificity 72.72%) between fast and slow progressors. Due to its neuroprotective properties, our data suggest that Gas6 could be an intriguing biomarker in ALS patients.

Keywords: Amyotrophic lateral sclerosis; Bulbar phenotype; Disease progression; Gas6/TAM receptors; Neurofilaments.

PubMed Disclaimer

Conflict of interest statement

Declarations. Ethics Approval: The study was performed in lines with principles of Declaration of Helsinki. Approval was granted by the Ethics Committee (CE 184/20) of AOU Maggiore della Carità, Novara. The study was conducted in accordance with the local legislation and institutional requirements. The participants provided their written informed consent to participate in this study. Competing Interests: The authors declare no competing interests.

References

    1. Keon M, Musrie B, Dinger M et al (2021) Destination amyotrophic lateral sclerosis. Front Neurol 12:596006. https://doi.org/10.3389/fneur.2021.596006
    1. Chio A, Moglia C, Canosa A et al (2020) ALS phenotype is influenced by age, sex, and genetics: a population-based study. Neurol 94(8):e802–e810. https://doi.org/10.1212/WNL.0000000000008869
    1. D’amico E, Pasmantier M, Lee YW et al (2013) Clinical evolution of pure upper motor neuron disease/dysfunction (PUMMD). Muscle Nerve 47(1):28–32. https://doi.org/10.1002/mus.23496
    1. Gordon PH, Cheng B, Katz IB et al (2009) Clinical features that distinguish PLS, upper motor neuron-dominant ALS, and typical ALS. Neurol 72(22):1948–1952. https://doi.org/10.1212/WNL.0b013e3181a8269b
    1. Masrori P, Van Damme P (2020) Amyotrophic lateral sclerosis: a clinical review. Eur J Neurol 27(10):1918–1929 - PubMed

Substances

LinkOut - more resources