Circulating Neurofilament Light Predicts Cognitive Decline in Patients With Post-stroke Subjective Cognitive Impairment

Wang, Jianhong; Huang, Jie; Guo, Feifei; Wang, Fang; Yang, Shu; Yu, Neng-Wei; Zheng, Bo; Wang, Jian

doi:10.3389/fnagi.2021.665981

Cited by 10 publications

(13 citation statements)

References 21 publications

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“…Elevated plasma NfL was also associated with poor functional outcome and mortality rate after spontaneous subarachnoid hemorrhage ( Hviid et al, 2020a ). The elevated NfL levels continued at the 3-month follow-up and seemed to return to normal at 15-month after stroke, indicating that levels of NfL could be a tool for monitoring infarct extent ( Tiedt et al, 2018 ), predicting cognitive function ( Peng et al, 2021 ; Wang J.H. et al, 2021 ) and mortality in patients with stroke ( Gendron et al, 2020 ).…”

Section: Properties Of Neurofilaments Relevant To Their Use As Biomarkersmentioning

confidence: 99%

Neurofilament Proteins as Biomarkers to Monitor Neurological Diseases and the Efficacy of Therapies

2021

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Biomarkers of neurodegeneration and neuronal injury have the potential to improve diagnostic accuracy, disease monitoring, prognosis, and measure treatment efficacy. Neurofilament proteins (NfPs) are well suited as biomarkers in these contexts because they are major neuron-specific components that maintain structural integrity and are sensitive to neurodegeneration and neuronal injury across a wide range of neurologic diseases. Low levels of NfPs are constantly released from neurons into the extracellular space and ultimately reach the cerebrospinal fluid (CSF) and blood under physiological conditions throughout normal brain development, maturation, and aging. NfP levels in CSF and blood rise above normal in response to neuronal injury and neurodegeneration independently of cause. NfPs in CSF measured by lumbar puncture are about 40-fold more concentrated than in blood in healthy individuals. New ultra-sensitive methods now allow minimally invasive measurement of these low levels of NfPs in serum or plasma to track disease onset and progression in neurological disorders or nervous system injury and assess responses to therapeutic interventions. Any of the five Nf subunits – neurofilament light chain (NfL), neurofilament medium chain (NfM), neurofilament heavy chain (NfH), alpha-internexin (INA) and peripherin (PRPH) may be altered in a given neuropathological condition. In familial and sporadic Alzheimer’s disease (AD), plasma NfL levels may rise as early as 22 years before clinical onset in familial AD and 10 years before sporadic AD. The major determinants of elevated levels of NfPs and degradation fragments in CSF and blood are the magnitude of damaged or degenerating axons of fiber tracks, the affected axon caliber sizes and the rate of release of NfP and fragments at different stages of a given neurological disease or condition directly or indirectly affecting central nervous system (CNS) and/or peripheral nervous system (PNS). NfPs are rapidly emerging as transformative blood biomarkers in neurology providing novel insights into a wide range of neurological diseases and advancing clinical trials. Here we summarize the current understanding of intracellular NfP physiology, pathophysiology and extracellular kinetics of NfPs in biofluids and review the value and limitations of NfPs and degradation fragments as biomarkers of neurodegeneration and neuronal injury.

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Section: Properties Of Neurofilaments Relevant To Their Use As Biomarkersmentioning

confidence: 99%

Neurofilament Proteins as Biomarkers to Monitor Neurological Diseases and the Efficacy of Therapies

2021

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“…Mounting evidence has demonstrated the association between circulating NfL levels and functional outcomes of AIS (10,20). NfL is also suggested to be a reliable biomarker predicting post-stroke cognitive impairment (11,21,22). Mental health disorders, including depression, anxiety and insomnia, are commonly observed during the rehabilitation of AIS (23)(24)(25).…”

Section: Discussionmentioning

confidence: 99%

“…This study used the same cohort of patients in our previous study (11). Briefly, inpatients with AIS from the Department of Neurology, Sichuan Provincial People's Hospital and Ya'an People's Hospital during May 1, 2016 and Dec 31, 2019, were screened for eligibility for this study.…”

Section: Patientsmentioning

confidence: 99%

“…Accordingly, the 9item Patient Health Questionnaire (PHQ-9; range, 0-27) (13), the 7-item Generalized Anxiety Disorder (GAD-7) scale (range, 0-21) ( 14), the 7-item Insomnia Severity Index (ISI; range, 0-28) (15), were used to assess the severity of symptoms of depression, anxiety, and insomnia, respectively. The total scores of these measurement tools were interpreted as follows: PHQ-9, normal (0-4), mild (5-9), moderate (10)(11)(12)(13)(14), and severe (15)(16)(17)(18)(19)(20)(21)(22)(23)(24)(25)(26)(27) depression; GAD-7, normal (0-4), mild (5-9), moderate (10)(11)(12)(13)(14), and severe (15)(16)(17)(18)(19)(20)(21) anxiety; ISI, normal (0-7), subthreshold (8)(9)(10)(11)(12)(13)(14), moderate (15)(16)(17)(18)(19)(20)(21), and severe (22)…”

Section: Assessment Of Mental Health Outcomesmentioning

confidence: 99%

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Serum Neurofilament Light Predicts 6-Month Mental Health Outcomes in a Cohort of Patients With Acute Ischemic Stroke

Wang

Guo

et al. 2022

Front. Psychiatry

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BackgroundMental health problems after acute ischemic stroke (AIS) have caused wide public concerns, and the study on early identification of these disorders is still an open issue. This study aims to investigate the predictive effect of circulating neurofilament light (NfL) on long-term mental health status of AIS patients.MethodsThis study collected demographic information and mental health measurements from 304 AIS patients from May 1, 2016 to Dec 31, 2019. Baseline serum neurofilament light (NfL) was determined within 2 h since patient admission. Six months after AIS onset, the degree of symptoms of depression, anxiety, and insomnia was assessed by the Chinese versions of the 9-item Patient Health Questionnaire (PHQ-9), the 7-item Generalized Anxiety Disorder scale (GAD-7), the 7-item Insomnia Severity Index (ISI), respectively. Subjects were divided into the high NfL group and the low NfL group. Multivariate logistic regression analysis was performed to identify factors associated with these mental health problems.ResultsThe high NfL group had significantly higher PHQ-9, GAD-7, and ISI scores than the low NfL group. The prediction of serum NfL for major depression generated a sensitivity of 70.27%, a specificity of 67.79% and an AUC of 0.694. The prediction of serum NfL for anxiety generated a sensitivity of 69.23%, a specificity of 64.02%, and an AUC of 0.683. The prediction of serum NfL for insomnia generated a sensitivity of 75.00%, a specificity of 66.43% and an AUC of 0.723. Higher serum NfL was a risk factor of post-AIS depression [ORs (95% CI): 4.427 (1.918, 10.217)], anxiety [ORs (95% CI): 3.063 (1.939, 6.692)], and insomnia [ORs (95% CI): 4.200 (1.526, 11.562)].ConclusionsThese findings imply that circulating NfL might be a potential biomarker of long-term mental health problems after AIS.

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“…With the development of critical medicine, the death rate of stroke has been significantly decreased (Zhao et al 2021). It has been confirmed that stroke can result in cognitive impairment also known as post-stroke cognitive impairment (Shih et al 2013;Wang et al 2021). However, covered by severe physical disability, post-stroke cognitive impairment is likely to be ignored in most cases (Kwon et al 2020;Sun et al 2014).…”

Section: Introductionmentioning

confidence: 99%

MiR-1224 downregulation inhibits OGD/R-induced hippocampal neuron apoptosis through targeting Ku protein

Wan

Xiao

2021

Metab Brain Dis

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Ischemic cerebrovascular disease is the main cause of disability due to stroke. This study aimed to investigate the function of miR-1224 in OGD/R-induced hippocampal neuron apoptosis, as well as the regulatory mechanism of miR-1224 in ischemic cerebrovascular disease. The oxygen-glucose deprivation/reperfusion (OGD/R) model of primary mouse hippocampal neurons was established. RT-qPCR detected miR-1224, Ku70 and Ku86 levels. Western blotting was applied to measure the expression of Ku70/86 and apoptosis related proteins. Flow cytometry was used to assess apoptosis. JC-1 fluorescence was performed to test the mitochondrial membrane potential (MMP) in neurons. The double luciferase reporter assay was performed to investigate the relationship between miR-1224 and Ku70/86. OGD/R induced the apoptosis and mitochondrial injury in neuronal cells, while miR-1224 downregulation or Ku70/86 upregulation reversed this phenomenon. Meanwhile, miR-1224 negatively regulated the expression of Ku70/86 in neuronal cells through directly targeting Ku70/86. Furthermore, knockdown of Ku70/86 significantly reversed the inhibitory effect of miR-1224 silencing on apoptosis and mitochondrial injury in OGD/R-treated neuronal cells. Our findings indicated that miR-1224 downregulation suppressed OGD/R-induced hippocampal neuron apoptosis by targeting Ku protein, suggesting that miR-1224 could serve as a new target for ischemic cerebrovascular disease treatment.

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Circulating Neurofilament Light Predicts Cognitive Decline in Patients With Post-stroke Subjective Cognitive Impairment

Cited by 10 publications

References 21 publications

Neurofilament Proteins as Biomarkers to Monitor Neurological Diseases and the Efficacy of Therapies

Neurofilament Proteins as Biomarkers to Monitor Neurological Diseases and the Efficacy of Therapies

Serum Neurofilament Light Predicts 6-Month Mental Health Outcomes in a Cohort of Patients With Acute Ischemic Stroke

MiR-1224 downregulation inhibits OGD/R-induced hippocampal neuron apoptosis through targeting Ku protein

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