Serum ADMA Level as a Prognostic Biomarker for Amyotrophic Lateral Sclerosis

Diagnostic form with diagnosis Amyotrophic lateral sclerosis (ALS) and pills.
Researchers sought to investigate the association between serum asymmetric dimethylarginine (ADMA) levels and the progression and prognosis of amyotrophic lateral sclerosis, and to compare cerebrospinal fluid and serum ADMA levels with other ALS biomarkers.

Serum asymmetric dimethylarginine (ADMA) level is an independent biomarker of disease progression and prognosis in amyotrophic lateral sclerosis (ALS), according to a study published in the European Journal of Neurology.

ALS is a neurodegenerative disease with no known cure or pathogenesis. Recent research suggests protein arginine dimethylation is unregulated in the spinal cord of patients with ALS and cerebrospinal fluid (CSF) levels of ADMA could potentially be a prognostic biomarker of ALS disease progression and prognosis, the researchers explained. The objective of the current study was to investigate the association between ADMA levels and the progression and prognosis of ALS, and to compare CSF and serum ADMA levels with other ALS biomarkers.

Researchers evaluated changes in serum ADMA levels in patients with ALS and the correlation of ADMA levels with neurofilament light chain (NfL) levels to determine how ADMA is associated with ALS pathology.

Eligible participants were diagnosed with ALS or followed up for ALS at a hospital in Japan from July 2016 to August 2020. A total of 68 patients with ALS were included, along with 54 disease control patients with Parkinson disease other neurologic disorders and 20 healthy control individuals. ADMA was measured with use of a high-performance liquid chromatography tandem mass spectrometry system.

In the overall cohort, participants’ average age at venipuncture (ALS patients, 63.5 [47.5-79.5] years; disease control patients, 63.0 [47.75-78.25] years; healthy control individuals, 59.0 [45.0-74.0] years) and sex ratio (male:female, ALS patients, 41:27; disease control patients, 32:22; and healthy control individuals, 12:8) were not significantly different among the 3 groups.

Patients with ALS had significantly higher serum ADMA levels compared with healthy control individuals and disease control patients (ALS vs healthy control individuals, P <.0001; ALS vs disease control patients, P =.006). Disease control patients had slightly higher ADMA levels vs healthy control individuals, although the difference was not statistically significant (P =.051).

Serum ADMA levels were significantly correlated with CSF levels (r = 0.591, P <.032). No correlation was observed in l-arginine level between serum and CSF (r = 0.591, P <.032).

Serum ADMA level was strongly correlated with disease progression (ALS Functional Rating Scale Revised [ALSFRS-R] pre-slope) (r = 0.505; P <.0001) but not with disease severity at each time point (ALSFRS-R) (r = −0.261; P =.032), age (r = 0.138; P =.241), or disease duration at venipuncture (r = −0.286, P =.017).

Plasma NfL levels were then measured to analyze the degree of neurodegeneration, and ADMA level was significantly correlated with NfL level (r = 0.430, P =.002). ADMA level was not correlated with nitric oxide level (r = 0.270, P =.080), which suggests that the increase in ADMA level was independent of nitric oxide dysregulation, according to the researchers.

Among several study limitations, the number of patients enrolled was small and alterations in ADMA levels need to be further evaluated in other neurologic disorders to conclude the specificity of this biomarker in ALS. Furthermore, the pathomechanism by which an increased ADMA level affects disease progression is unclear.

“Interestingly, serum ADMA levels did not change significantly over time, indicating that serum ADMA is not the consequence of disease progression but rather reflects the upstream of the disease,” the researchers concluded.


Ikenaka K, Maeda Y, Hott Y, et al. Serum asymmetric dimethylarginine level correlates with the progression and prognosis of amyotrophic lateral sclerosis. Eur J Neurol. Published online January 19, 2022. doi: 10.1111/ene.15254