Elevated neurofilament light chain (NFL) mRNA levels in prediabetic peripheral neuropathy

Çelikbilek, Asuman; Tanık, Nermin; Sabah, Seda; Börekçi, Elif; Akyol, Lutfi; Ak, Hakan; Adam, Mehmet; Süher, Murat; Yılmaz, Neziha

doi:10.1007/s11033-014-3270-y

Cited by 20 publications

(27 citation statements)

References 29 publications

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“…Recently, another study showed that the mRNA levels of NfL (also known as NEFL) in the blood of individuals with impaired glucose tolerance displayed a positive correlation with the severity of DPN [33].…”

Section: Discussionmentioning

confidence: 99%

“…In a study in individuals with diabetic retinopathy, whole blood mRNA levels of rhodopsin have been shown to reflect a benefit in differentiating the stages of the disease [ 14 ]. Recently, another study showed that the mRNA levels of NfL (also known as NEFL ) in the blood of individuals with impaired glucose tolerance displayed a positive correlation with the severity of DPN [ 33 ].…”

Section: Discussionmentioning

confidence: 99%

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Neuron-specific biomarkers predict hypo- and hyperalgesia in individuals with diabetic peripheral neuropathy

et al. 2021

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Aims/hypothesis The individual risk of progression of diabetic peripheral neuropathy is difficult to predict for each individual. Mutations in proteins that are responsible for the process of myelination are known to cause neurodegeneration and display alteration in experimental models of diabetic neuropathy. In a prospective observational human pilot study, we investigated myelin-specific circulating mRNA targets, which have been identified in vitro, for their capacity in the diagnosis and prediction of diabetic neuropathy. The most promising candidate was tested against the recently established biomarker of neural damage, neurofilament light chain protein. Methods Schwann cells were cultured under high-glucose conditions and mRNAs of various myelin-specific genes were screened intra- and extracellularly. Ninety-two participants with type 2 diabetes and 30 control participants were enrolled and evaluated for peripheral neuropathy using neuropathy deficit scores, neuropathy symptom scores and nerve conduction studies as well as quantitative sensory testing at baseline and after 12/24 months of a follow-up period. Magnetic resonance neurography of the sciatic nerve was performed in 37 individuals. Neurofilament light chain protein and four myelin-specific mRNA transcripts derived from in vitro screenings were measured in the serum of all participants. The results were tested for associations with specific neuropathic deficits, fractional anisotropy and the progression of neuropathic deficits at baseline and after 12 and 24 months. Results In neuronal Schwann cells and human nerve sections, myelin protein zero was identified as the strongest candidate for a biomarker study. Circulating mRNA of myelin protein zero was decreased significantly in participants with diabetic neuropathy (p < 0.001), whereas neurofilament light chain protein showed increased levels in participants with diabetic neuropathy (p < 0.05). Both variables were linked to altered electrophysiology, fractional anisotropy and quantitative sensory testing. In a receiver-operating characteristic curve analysis myelin protein zero improved the diagnostic performance significantly in combination with a standard model (diabetes duration, age, BMI, HbA1c) from an AUC of 0.681 to 0.836 for the detection of diabetic peripheral neuropathy. A follow-up study revealed that increased neurofilament light chain was associated with the development of a hyperalgesic phenotype (p < 0.05), whereas decreased myelin protein zero predicted hypoalgesia (p < 0.001) and progressive loss of nerve function 24 months in advance (HR of 6.519). Conclusions/interpretation This study introduces a dynamic and non-invasive assessment strategy for the underlying pathogenesis of diabetic peripheral neuropathy. The diagnosis of axonal degeneration, associated with hyperalgesia, and demyelination, linked to hypoalgesia, could benefit from the usage of neurofilament light chain protein and circulating mRNA of myelin protein zero as potential biomarkers. Graphical abstract

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Neuron-specific biomarkers predict hypo- and hyperalgesia in individuals with diabetic peripheral neuropathy

et al. 2021

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“…The limited sample size does not allow for reliable estimation of the amount of deviation from normal individuals, particularly beyond the 90th percentile. This model did not account for potential comorbidities associated with older age (e.g., cardiovascular disease, 41 diabetes 42 , and cognitive impairment) or other factors that could impact NfL levels (e.g., body weight, normalized brain volume). This model was developed using NfL data analyzed on the SIMOA platform, and additional investigation is needed to understand generalizability to data collected on other platforms.…”

Section: Discussionmentioning

confidence: 99%

Development of an age‐adjusted model for blood neurofilament light chain

Harp¹,

Thanei

Jia³

et al. 2022

Ann Clin Transl Neurol

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Objective To develop an age‐adjustment model for neurofilament light chain (NfL), an emerging injury marker in patients with a range of neurologic conditions including multiple sclerosis (MS). Methods Serum and plasma samples were collected from a healthy donor (HD) cohort of 118 individuals aged 24 to 66 years, 90 patients with relapsing MS (RMS) and 22 patients with progressive MS (PMS). Serum and plasma samples were assessed for NfL using the SIMOA assay (Quanterix NfL Advantage Kit™). A log‐linear model was used to evaluate the relationship between NfL and age and to calculate age‐adjusted NfL levels. Results Higher serum and plasma NfL levels were significantly associated with increasing HD age. Log‐transformation of blood NfL levels reduced heteroscedasticity and skewness. A log‐linear model enabled adjustment for age‐related increase in serum and plasma NfL levels (2.3% [95% CI, 1.6–2.9] and 2.6% [95% CI, 1.3–3.3] per year, respectively). Following age adjustment, NfL did not show significant association with HD sex or ethnicity. While unadjusted serum NfL levels were elevated in patients with PMS (mean age 56 years) compared with those with RMS (mean age 37 years), age‐adjusted NfL levels did not differ. Interpretation A log‐linear, age adjustment model was developed to enable comparison of NfL levels across populations with different ages. While additional data and evidence are needed for patient‐level adoption, this could be a valuable tool for interpreting NfL levels across a range of patient groups with neurologic conditions.

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“…Plasma NfL levels were also inversely associated with brain glucose metabolism, longitudinally in the highly characterized Alzheimer’s Disease Neuroimaging Initiative (ADNI cohort) ( 23 ). A previous report indicated a positive correlation between NfL mRNA levels and Douleur Neuropathique 4 questionnaire score in pre-diabetic patients, indicating an early detection marker of pre-diabetic peripheral neuropathy ( 24 ). Therefore, plasma levels of NfL may be an attractive indicator of neurodegeneration in people with different glycaemic status.…”

Section: Introductionmentioning

confidence: 92%

Association of Plasma Neurofilament Light Chain With Glycaemic Control and Insulin Resistance in Middle-Aged Adults

et al. 2022

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AimsThis study aimed to determine the association of plasma neurofilament light (NfL), a marker of neurodegeneration, with diabetes status and glycaemic parameters in people with normal glycaemia (NG), pre-diabetes (PD) and type 2 diabetes (T2D).MethodsClinical and descriptive data for the diagnostic groups, NG (n=30), PD (n=48) and T2D (n=29), aged between 40 and 75 years were included in this cross-sectional analysis. Plasma NfL levels were analyzed using the ultra-sensitive single-molecule array (Simoa) platform.ResultsA positive correlation was evident between plasma NfL and fasting glucose (r = 0.2824; p = 0.0032). Plasma NfL levels were not correlated with fasting insulin and insulin resistance. Plasma Nfl levels were significantly different across the diabetes groups (T2D >PD >NG, p=0.0046). Post-hoc analysis indicated significantly higher plasma NfL levels in the T2D [12.4 (5.21) pg/mL] group than in the PD [10.2 (4.13) pg/mL] and NG [8.37 (5.65) pg/mL] groups. The relationship between diabetes status and NfL remained significant after adjusting for age, sex, BMI, HOMA-IR and physical activity (adjusted r2 = 0.271, p = 0.035).ConclusionsThese results show biomarker evidence of neurodegeneration in adults at risk or with T2D. Larger sample size and longitudinal analysis are required to better understand the application of NfL in people with risk and overt T2D.

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Elevated neurofilament light chain (NFL) mRNA levels in prediabetic peripheral neuropathy

Cited by 20 publications

References 29 publications

Neuron-specific biomarkers predict hypo- and hyperalgesia in individuals with diabetic peripheral neuropathy

Neuron-specific biomarkers predict hypo- and hyperalgesia in individuals with diabetic peripheral neuropathy

Development of an age‐adjusted model for blood neurofilament light chain

Association of Plasma Neurofilament Light Chain With Glycaemic Control and Insulin Resistance in Middle-Aged Adults

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