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

Thota, Rohith N.; Chatterjee, Pratishtha; Pedrini, Steve; Hone, Eugene; Ferguson, Jessica J. A.; Garg, Manohar L.; Martins, Ralph N.

doi:10.3389/fendo.2022.915449

Cited by 9 publications

(6 citation statements)

References 51 publications

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“…NfL levels might be impacted by medical comorbidities that are common among elders, complicating its utility as a biomarker. Although multiple sclerosis, neurodegenerative dementia, stroke, amyotrophic lateral sclerosis (Khalil et al, 2018), orthostatic hypotension (Park et al, 2021), hearing disorder (Park et al, 2016;Han et al, 2018), depression and anxiety disorders (Tauil et al, 2021), diabetes (Thota et al, 2022), psoriasis (Nowowiejska et al, 2022), transient ischemic attack (TIA;De Marchis et al, 2018) and sleep disorder (Jennum et al, 2017;Lysen et al, 2020;Targa et al, 2021) might impact NfL levels, we still found consistent results after adjusting for medical comorbidities. CSF NfL can purposefully play the role of a future candidate for CSF biomarkers when cognitive disorder risk is estimated among patients with PD (Hoops et al, 2009).…”

Section: Discussionsupporting

confidence: 62%

Cerebrospinal fluid neurofilament dynamic profiles predict cognitive progression in individuals with de novo Parkinson’s disease

Sheng

Liu

et al. 2022

Front. Aging Neurosci.

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BackgroundNeurofilament light chain protein (NfL) in cerebrospinal fluid (CSF) reflects the severity of neurodegeneration, with its altered concentrations discovered in Parkinson’s disease (PD) and Parkinson’s disease dementia (PD-D).ObjectiveTo determine whether CSF NfL, a promising biomarker of neuronal/axonal damage, can be used to monitor cognitive progression in de novo Parkinson’s disease and predict future cognitive decline.MethodsA total of 259 people were recruited in this study, including 85 healthy controls (HC) and 174 neonatal PD patients from the Parkinson’s Progression Markers Initiative (PPMI). Multiple linear regression and linear mixed effects models were used to examine the associations of baseline/longitudinal CSF NfL with cognitive decline and other CSF biomarkers. Kaplan–Meier analysis and log-rank test were used to compare the cumulative probability risk of cognition progression during the follow-up. Multivariate cox regression was used to detect cognitive progression in de novo PD.ResultsWe found PD patients with mild cognitive impairment (PD-MCI) was higher than with normal cognition (PD-NC) in terms of CSF NfL baseline levels (p = 0.003) and longitudinal increase rate (p = 0.034). Both baseline CSF NfL and its rate of change predicted measurable cognitive decline in de novo PD (MoCA, β = −0.010, p = 0.011; β = −0.0002, p < 0.001, respectively). The predictive effects in de novo PD patients aged >65, male, ill-educated (<13 years) and without carrying Apolipoprotein E ε4 (APOE ε4) seemed to be more obvious and reflected in more domains investigated. We also observed that CSF NfL levels predicted progression in de novo PD patients with different cognitive diagnosis and amyloid status. After an average follow-up of 6.66 ± 2.54 years, higher concentration above the median of baseline CSF NfL was associated with a future high risk of PD with dementia (adjusted HR 2.82, 95% CI: 1.11–7.20, p = 0.030).ConclusionOur results indicated that CSF NfL is a promising prognostic predictor of PD, and its concentration and dynamics can monitor the severity and progression of cognitive decline in de novo PD patients.

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Section: Discussionsupporting

confidence: 62%

Cerebrospinal fluid neurofilament dynamic profiles predict cognitive progression in individuals with de novo Parkinson’s disease

Sheng

Liu

et al. 2022

Front. Aging Neurosci.

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“…It is not completely clear if comorbidities may impact plasma NfL levels. There is some evidence that plasma NfL levels could be influenced by body mass index (BMI) [ 58 , 59 ], renal function [ 60 ], and diabetes [ 61 ]. However, as previously showed by Koini et al [ 62 ], the impact that comorbidities could have on plasma NfL levels is influenced by the age of the individual.…”

Section: Discussionmentioning

confidence: 99%

Neuro-Axonal Damage and Alteration of Blood–Brain Barrier Integrity in COVID-19 Patients

Zingaropoli

Iannetta

Piermatteo

et al. 2022

Cells

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Neurofilament light chain (NfL) is a specific biomarker of neuro-axonal damage. Matrix metalloproteinases (MMPs) are zinc-dependent enzymes involved in blood–brain barrier (BBB) integrity. We explored neuro-axonal damage, alteration of BBB integrity and SARS-CoV-2 RNA presence in COVID-19 patients with severe neurological symptoms (neuro-COVID) as well as neuro-axonal damage in COVID-19 patients without severe neurological symptoms according to disease severity and after recovery, comparing the obtained findings with healthy donors (HD). Overall, COVID-19 patients (n = 55) showed higher plasma NfL levels compared to HD (n = 31) (p < 0.0001), especially those who developed ARDS (n = 28) (p = 0.0005). After recovery, plasma NfL levels were still higher in ARDS patients compared to HD (p = 0.0037). In neuro-COVID patients (n = 12), higher CSF and plasma NfL, and CSF MMP-2 levels in ARDS than non-ARDS group were observed (p = 0.0357, p = 0.0346 and p = 0.0303, respectively). SARS-CoV-2 RNA was detected in four CSF and two plasma samples. SARS-CoV-2 RNA detection was not associated to increased CSF NfL and MMP levels. During COVID-19, ARDS could be associated to CNS damage and alteration of BBB integrity in the absence of SARS-CoV-2 RNA detection in CSF or blood. CNS damage was still detectable after discharge in blood of COVID-19 patients who developed ARDS during hospitalization.

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“…NfL levels were lower in Aβ− participants. As plasma NfL levels are associated with aging and diabetes mellitus (DM), 35 older age and higher prevalence of DM in our Aβ− participants may have led to these results. In the current study, NfL levels were higher in patients with DM, but p‐tau181, Aβ42, and Aβ40 were not (Table S6).…”

Section: Discussionmentioning

confidence: 65%

Predicting amyloid PET positivity using plasma p‐tau181 and other blood‐based biomarkers

Kwon,

Lee,

Kim

et al. 2023

Alz & Dem Diag Ass & Dis Mo

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IntroductionThis study aimed to determine the efficacy of combining plasma phosphorylated tau (p‐tau)181, amyloid beta (Aβ)42/Aβ40, neurofilament light (NfL), and apolipoprotein E (APOE) genotypes for detecting positive amyloid positron emission tomography (PET), which is little known in the Asian population, in two independent cohorts.MethodsBiomarkers were measured using a single‐molecule array (Simoa) in a cohort study (Asan). All participants underwent amyloid PET. Significant changes in the area under the curve (AUC) and Akaike Information Criterion values were considered to determine the best model. The generalizability of this model was tested using another cohort (KBASE‐V).ResultsIn the Asan cohort, after adjusting for age and sex, p‐tau181 (AUC = 0.854) or APOE ε4 status (AUC = 0.769) distinguished Aβ status with high accuracy. Combining them or adding NfL and Aβ42/40 improved model fitness. The best‐fit model included the plasma p‐tau181, APOE ε4, NfL and Aβ42/40. The models established from the Asan cohort were tested in the KBASE‐V cohort. Additionally, in the KBASE‐V cohort, these three biomarker models had similar AUC in cognitively unimpaired (AUC = 0.768) and mild cognitive impairment (MCI) (AUC = 0.997) participants.ConclusionsPlasma p‐tau181 showed a high performance in determining Aβ‐PET positivity. Adding plasma NfL and APOE ε4 status improved the model fit without significant improvement in AUC.

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

Cited by 9 publications

References 51 publications

Cerebrospinal fluid neurofilament dynamic profiles predict cognitive progression in individuals with de novo Parkinson’s disease

Cerebrospinal fluid neurofilament dynamic profiles predict cognitive progression in individuals with de novo Parkinson’s disease

Neuro-Axonal Damage and Alteration of Blood–Brain Barrier Integrity in COVID-19 Patients

Predicting amyloid PET positivity using plasma p‐tau181 and other blood‐based biomarkers

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