scholarly journals Assessment of Plasma Neurofilament Light as a Biomarker of Neuronal Injury in Young Adults with Perinatal HIV Infection

2021 ◽  
Author(s):  
Beatriz Ruiz-Saez ◽  
Manuela Martín-Bejarano ◽  
Ana Martínez Aragon ◽  
Magnus Gisslen ◽  
Henrik Zetterberg ◽  
...  
Keyword(s):  
Young Adults ◽  
Viral Load ◽  
White Matter ◽  
Single Molecule ◽  
Fluid Intelligence ◽  
Cns Injury ◽  
Cross Sectional ◽  
Neurofilament Light ◽  
Brain Volumes ◽  
Perinatal Hiv

Abstract Background: Higher plasma concentration of neurofilament light (pNfL) is associated with neurodegeneration. However, to our knowledge, up to now, there are no data in HIV patients with infection due to vertical transmission. This is the first study to report pNfL in a cohort of HIV perinatally infected (PHIV) young adults compared with non-HIV (HIV-) controls.Methods: Thirty-three PHIV patients and 25 age-matched HIV- were recruited to this cross-sectional study. Plasma NfL concentrations were compared between both groups. In a subgroup of 48 participants (25 PHIV patients and 23 HIV-), brain volumes through magnetic resonance imaging (MRI) and neuropsychological testing (NT), were also conducted and compared with pNfL values.Plasma NfL concentration was measured using Single Molecule Array (Simoa) immunoassay.NT included fluid intelligence and processing speed through the WAIS-IV Coding subtest, and the Stroop Test.ResultsFifty-eight participants were included, median age 20.7 years [IQR 17.8-23.4]. 100% of the patients were under antiretroviral treatment (cART) and 85% had viral load <50 copies/ml.Although no statistically significant differences were found between patients and controls regarding pNfL concentration, there was a trend towards higher levels in patients with viral load >50 copies/ml.With regard to brain volumes and NT, in the PHIV group, lower white matter volumes and lower score in the coding subtest were associated with higher pNfL values. ConclusionsMost PHIV adolescents under cART have similar levels of pNfL than HIV-. As reported in adults, those with HIV-RNA >50 copies/ml showed higher values and lower white matter volumes that may imply an ongoing CNS injury. Plasma NfL could be a feasible biomarker of CNS injury in PHIV patients with unsuppressed viral load.

scholarly journals Neurochemical evidence of astrocytic and neuronal injury commonly found in COVID-19

Neurology ◽  
2020 ◽  
Vol 95 (12) ◽  
pp. e1754-e1759 ◽  
Author(s):  
Nelly Kanberg ◽  
Nicholas J. Ashton ◽  
Lars-Magnus Andersson ◽  
Aylin Yilmaz ◽  
Magnus Lindh ◽  
...  
Keyword(s):  
Single Molecule ◽  
Severe Disease ◽  
Plasma Concentrations ◽  
Neuronal Injury ◽  
Cns Injury ◽  
Neurofilament Light Chain ◽  
Cross Sectional ◽  
Neurofilament Light ◽  
Plasma Biomarkers

ObjectiveTo test the hypothesis that coronavirus disease 2019 (COVID-19) has an impact on the CNS by measuring plasma biomarkers of CNS injury.MethodsWe recruited 47 patients with mild (n = 20), moderate (n = 9), or severe (n = 18) COVID-19 and measured 2 plasma biomarkers of CNS injury by single molecule array, neurofilament light chain protein (NfL; a marker of intra-axonal neuronal injury) and glial fibrillary acidic protein (GFAp; a marker of astrocytic activation/injury), in samples collected at presentation and again in a subset after a mean of 11.4 days. Cross-sectional results were compared with results from 33 age-matched controls derived from an independent cohort.ResultsThe patients with severe COVID-19 had higher plasma concentrations of GFAp (p = 0.001) and NfL (p < 0.001) than controls, while GFAp was also increased in patients with moderate disease (p = 0.03). In patients with severe disease, an early peak in plasma GFAp decreased on follow-up (p < 0.01), while NfL showed a sustained increase from first to last follow-up (p < 0.01), perhaps reflecting a sequence of early astrocytic response and more delayed axonal injury.ConclusionWe show neurochemical evidence of neuronal injury and glial activation in patients with moderate and severe COVID-19. Further studies are needed to clarify the frequency and nature of COVID-19–related CNS damage and its relation to both clinically defined CNS events such as hypoxic and ischemic events and mechanisms more closely linked to systemic severe acute respiratory syndrome coronavirus 2 infection and consequent immune activation, as well as to evaluate the clinical utility of monitoring plasma NfL and GFAp in the management of this group of patients.

scholarly journals Plasma tau is increased in frontotemporal dementia

2018 ◽  
Vol 89 (8) ◽  
pp. 804-807 ◽  
Author(s):  
Martha S Foiani ◽  
Ione OC Woollacott ◽  
Carolin Heller ◽  
Martina Bocchetta ◽  
Amanda Heslegrave ◽  
...  
Keyword(s):  
Frontotemporal Dementia ◽  
Single Molecule ◽  
Neurodegenerative Disorder ◽  
Primary Progressive Aphasia ◽  
Personality Change ◽  
Neurofilament Light Chain ◽  
Cross Sectional ◽  
Neurofilament Light ◽  
Brain Volumes ◽  
Genetic Groups

BackgroundFrontotemporal dementia (FTD) is a heterogeneous neurodegenerative disorder presenting clinically with personality change (behavioural variant FTD (bvFTD)) or language deficits (primary progressive aphasia (PPA)). About a third of FTD is familial with mutations in GRN, MAPT and C9orf72 being the major genetic causes. Robust biomarkers of the underlying pathology are still lacking in FTD with no markers currently being able to distinguish those with tau and TDP-43 inclusions during life.MethodsThis study used an ultrasensitive single molecule methodology to measure plasma tau concentrations in 176 participants: 71 with bvFTD, 83 with PPA and 22 healthy controls. The patient group included 36 with pathogenic mutations in either MAPT (n=12), GRN (n=9) or C9orf72 (n=15). Group comparisons were performed between clinical and genetic groups and controls using a linear regression model with bias-corrected bootstrap CIs. Correlative analyses were performed to investigate associations with measures of disease severity and progression.ResultsHigher plasma tau concentrations were seen in bvFTD (mean 1.96 (SD 1.07) pg/mL) and PPA (2.65 (2.15) pg/mL) compared with controls (1.67 (0.50) pg/mL). Investigating the PPA group further showed significantly higher levels compared with controls in each of the PPA subtypes (non-fluent, semantic and logopenic variants, as well as a fourth group not meeting criteria for one of the three main variants). In the genetic groups, only the MAPT group had significantly increased concentrations (2.62 (1.39) pg/mL) compared with controls. No significant correlations were seen with cross-sectional or longitudinal brain volumes, serum neurofilament light chain concentrations or disease duration.ConclusionPlasma tau levels are increased in FTD in all clinical groups, but in the genetic subtypes only in MAPT mutations, the group of patients who definitively have tau pathology at postmortem. Future studies will be required in pathologically confirmed cohorts to investigate this association further, and whether plasma tau will be helpful in differentiating patients with FTD with tau from those with other pathologies.

scholarly journals Blood neurofilament light concentration at admittance: a potential prognostic marker in COVID-19

2021 ◽  
Author(s):  
Anne Hege Aamodt ◽  
Einar August Høgestøl ◽  
Trine Haug Popperud ◽  
Jan Cato Holter ◽  
Anne Ma Dyrhol-Riise ◽  
...  
Keyword(s):  
Nervous System ◽  
Single Molecule ◽  
Linear Models ◽  
Clinical Signs ◽  
Repeated Measurements ◽  
Cns Injury ◽  
Serum Concentrations ◽  
Blood Biomarkers ◽  
Neurofilament Light Chain ◽  
Neurofilament Light

Abstract Objective To test the hypotheses that blood biomarkers for nervous system injury, serum concentrations of neurofilament light chain protein (NfL) and glial fibrillary acidic protein (GFAp) can serve as biomarkers for disease severity in COVID-19 patients. Methods Forty-seven inpatients with confirmed COVID-19 had blood samples drawn on admission for assessing serum biomarkers of CNS injury by Single molecule array (Simoa), NfL and GFAp. Concentrations of NfL and GFAp were analyzed in relation to symptoms, clinical signs, inflammatory biomarkers and clinical outcomes. We used multivariate linear models to test for differences in biomarker concentrations in the subgroups, accounting for confounding effects. Results In total, 21% (n = 10) of the patients were admitted to an intensive care unit, and the overall mortality rate was 13% (n = 6). Non-survivors had higher serum concentrations of NfL (p < 0.001) upon admission than patients who were discharged alive both in adjusted analyses (p = 2.6 × 10–7) and unadjusted analyses (p = 0.001). The concentrations of NfL in non-survivors increased over repeated measurements; whereas, the concentrations in survivors were stable. The GFAp concentration was also significantly higher in non-survivors than survivors (p = 0.02). Conclusion Increased concentrations of NfL and GFAp in COVID-19 patients on admission may indicate increased mortality risk. Measurement of blood biomarkers for nervous system injury can be useful to detect and monitor CNS injury in COVID-19.

scholarly journals Plasma Concentration of the Neurofilament Light Protein (NFL) is a Biomarker of CNS Injury in HIV Infection: A Cross-Sectional Study

EBioMedicine ◽  
2016 ◽  
Vol 3 ◽  
pp. 135-140 ◽  
Author(s):  
Magnus Gisslén ◽  
Richard W. Price ◽  
Ulf Andreasson ◽  
Niklas Norgren ◽  
Staffan Nilsson ◽  
...  
Keyword(s):  
Plasma Concentration ◽  
Hiv Infection ◽  
Cross Sectional Study ◽  
Cns Injury ◽  
Sectional Study ◽  
Cross Sectional ◽  
Neurofilament Light

scholarly journals Association of intrathecal pleocytosis and IgG synthesis with axonal damage in early MS

2020 ◽  
Vol 7 (3) ◽  
pp. e679 ◽  
Author(s):  
Sinah Engel ◽  
Falk Steffen ◽  
Timo Uphaus ◽  
Peter Scholz-Kreisel ◽  
Frauke Zipp ◽  
...  
Keyword(s):  
Single Molecule ◽  
Leukocyte Count ◽  
Cross Sectional Study ◽  
Axonal Damage ◽  
Oligoclonal Bands ◽  
Neurofilament Light Chain ◽  
Cross Sectional ◽  
Neurofilament Light ◽  
Igg Synthesis ◽  
Healthy Donors

ObjectiveTo investigate the association of serum neurofilament light chain (sNfL) levels with CSF parameters in clinically isolated syndrome (CIS) and early relapsing-remitting MS (RRMS), taking into account radiologic and clinical parameters of disease activity.MethodsSimultaneously collected serum and CSF samples of 112 untreated patients newly diagnosed with CIS or RRMS were included in this cross-sectional study. CSF parameters were obtained as part of routine diagnostic tests. sNfL levels of patients and of 62 healthy donors were measured by highly sensitive single molecule array (SiMoA) immunoassay.ResultsPatients with RRMS (n = 91, median 10.13 pg/mL, interquartile range [IQR] 6.67–17.77 pg/mL) had higher sNfL levels than healthy donors (n = 62, median 5.25 pg/mL, IQR 4.05–6.81 pg/mL, p < 0.001) and patients with CIS (n = 21, median 5.69 pg/mL, IQR 4.73–9.07 pg/mL, p < 0.001). Patients positive for oligoclonal bands (OCBs) (n = 101, median 9.19 pg/mL, IQR 6.34–16.38 pg/mL) had higher sNfL levels than OCB-negative patients (n = 11, median 5.93 pg/mL, IQR 2.93–8.56 pg/mL, p = 0.001). sNfL levels correlated with CSF immunoglobulin G (IgG) levels (r = 0.317, p = 0.002), IgG ratio (QIgG) (r = 0.344, p < 0.001), and CSF leukocyte count (r = 0.288, p = 0.002). In linear regression modeling, the CSF leukocyte count combined with the number of contrast-enhancing lesions in MRI predicted sNfL levels best.ConclusionsIn active MS, sNfL levels correlate with intrathecal pleocytosis and IgG synthesis, indicating that axonal damage is associated with both acute and chronic CNS-intrinsic inflammation.

scholarly journals Arterial stiffness and dementia pathology

Neurology ◽  
2018 ◽  
Vol 90 (14) ◽  
pp. e1248-e1256 ◽  
Author(s):  
Timothy M. Hughes ◽  
Lynne E. Wagenknecht ◽  
Suzanne Craft ◽  
Akiva Mintz ◽  
Gerardo Heiss ◽  
...  
Keyword(s):  
White Matter ◽  
Arterial Stiffness ◽  
Small Vessel Disease ◽  
Brain Mri ◽  
Volume Ratio ◽  
Cognitive Testing ◽  
White Matter Hyperintensity ◽  
Cross Sectional ◽  
Brain Volumes ◽  
Atherosclerosis Risk In Communities

ObjectiveArterial stiffness has been associated with evidence of cerebral small vessel disease (cSVD) and fibrillar β-amyloid (Aβ) deposition in the brain. These complex relationships have not been examined in racially and cognitively diverse cohorts.MethodsThe Atherosclerosis Risk in Communities (ARIC)–Neurocognitive Study collected detailed cognitive testing for adjudication of dementia and mild cognitive impairment (MCI), brain MRI, and arterial stiffness by pulse wave velocity (PWV, carotid-femoral [cfPWV] and heart-carotid [hcPWV]). The ARIC-PET ancillary study added Aβ imaging using florbetapir ([18F]-AV-45) to obtain standardized uptake volume ratios and defined global Aβ-positivity as standardized uptake volume ratio >1.2. One-SD increase in PWV was related to brain volume, MRI-defined cSVD (e.g., cerebral microbleeds and white matter hyperintensity), and cortical Aβ deposition adjusted for age, body mass index, sex, race, and APOE ε4 status. We examined the cross-sectional relationships including interactions by race, APOE ε4 status, and cognition.ResultsAmong the 320 ARIC-PET participants (76 [5] years, 45% black, 27% MCI), greater central stiffness (hcPWV) was associated with greater Aβ deposition (odds ratio [OR] = 1.31, 95% confidence interval [CI] 1.01–1.71). Greater central stiffness (cfPWV) was significantly associated with having lower brain volumes in Alzheimer disease–susceptible regions (in mm3, β = −1.5 [0.7 SD], p = 0.03) and high white matter hyperintensity burden (OR = 1.6, 95% CI 1.2–2.1). Furthermore, cfPWV was associated with a higher odds of concomitant high white matter hyperintensity and Aβ-positive scans (OR = 1.4, 95% CI 1.1–2.1). These associations were strongest among individuals with MCI and did not differ by race or APOE ε4 status.ConclusionsArterial stiffness, measured by PWV, is an emerging risk factor for dementia through its repeated relationships with cognition, cSVD, and Aβ deposition.

scholarly journals Plasma neurofilament light and cerebrospinal fluid biomarkers are associated with white matter damage in Alzheimer's disease

2020 ◽  
Author(s):  
Fardin Nabizadeh ◽  
Mohammad Balabandian ◽  
Mohammad Reza Rostami ◽  
Samuel Berchi Kankam
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
White Matter ◽  
Diffusion Tensor ◽  
Brain Regions ◽  
Csf Biomarkers ◽  
Cross Sectional ◽  
Neurofilament Light ◽  
Microstructural Changes ◽  
Cerebrospinal Fluid Biomarkers

Abstract The most replicated blood biomarker for monitoring Alzheimer’s disease is neurofilament light (NFL). Recent evidence revealed that the plasma level of the NFL has a strong predictive value in cognitive decline and is elevated in AD patients. The Diffusion Tensor Imaging (DTI) is understood to reflect white matter disruption, neurodegeneration largely, and synaptic damage in AD. However, there is no investigation of the association between plasma NFL and white matter microstructure integrity. we have investigated the cross-sectional associations of plasma NFL, CSF tau, p tau, and Aβ with white matter microstructural changes as measured by DTI in 92 mild cognitive impairment (MCI) participants. We investigated potential correlations of the DTI values of each region of the MNI atlas, with plasma NFL, CSF total tau, CSF p tau, and as well as CSF Aβ, separately using a partial correlation model controlled for the effect of age, sex and APOE ε4 genotype. Our findings revealed a significant correlation between plasma and CSF biomarkers with altered white matter microstructural changes in widespread brain regions. Plasma NFL has a negative correlation with FA and positive correlation with RD, AD, and MD values in different regions. Plasma NFL promises to be an early biomarker of microstructural changes in MCI and for MCI progression to AD.

Abstract MP46: Growth Factors Are Associated With Imaging Markers of Brain Aging in Young Adults

Circulation ◽  
2015 ◽  
Vol 131 (suppl_1) ◽  
Author(s):  
Claudia L Satizabal ◽  
Alexa Beiser ◽  
Jayandra J Himali ◽  
Rhoda Au ◽  
Philip A Wolf ◽  
...  
Keyword(s):  
Young Adults ◽  
Growth Factors ◽  
White Matter ◽  
Growth Factor ◽  
White Matter Hyperintensities ◽  
Brain Aging ◽  
Brain Mri ◽  
Blood Draw ◽  
Brain Volumes ◽  
Angiopoietin 2

Metabolic and vascular dysregulation are related to stroke, cognitive decline and dementia. Growth factor biomarkers of these processes, such as Insulin-like Growth Factor 1 (IGF1) and Vascular Endothelial Growth Factor (VEGF) have been associated with risk of neurodegeneration and stroke in middle-aged and older Framingham participants. Additionally, hepatocyte growth factor (HGF) and angiopoietin 2 are novel biomarkers of interest as they have been related to cardiovascular events. As abnormal brain changes probably start years before clinical symptoms, we hypothesize that circulating growth factors are related to MRI endophenotypes of brain aging. We included 1,877 individuals aged 46±8 years from the Framingham Study. Blood samples were collected during 2008-2011, and used to measure IGF1, VEGF, HGF, angiopoietin 2 and its receptor tyrosine kinase (TIE2). Participants underwent brain MRI examination (2009-2013) from which brain volumes and white matter hyperintensities were estimated. We related growth factor levels to brain MRI markers adjusting for age, sex, time between blood draw and MRI, and cardiovascular risk factors. Lower IGF1, as well as higher HGF and angiopoietin 2 levels were associated with higher ventricular volumes indicative of brain shrinkage. Higher TIE2 levels were associated with lower total brain and gray matter volumes, while higher angiopoietin 2 levels were associated with lower white matter volumes. Lower IGF1 levels were also associated with reduced hippocampal volumes. Finally, higher TIE2 levels were associated with larger white matter hyperintensities. Our results suggest that growth factors are associated with neurodegenerative and cerebrovascular markers of brain aging in healthy young adults. Whereas IGF1 seems protective, higher levels of HGF, angiopoietin 2 and TIE2 were associated with greater subclinical brain injury. These associations expand our understanding of the earliest stages of brain aging. We will extend our findings by analyzing cognitive outcomes.

scholarly journals Higher Blood Pressure is Associated with Greater White Matter Lesions and Brain Atrophy: A Systematic Review with Meta-Analysis

2021 ◽  
Vol 10 (4) ◽  
pp. 637
Author(s):  
Khawlah Alateeq ◽  
Erin I. Walsh ◽  
Nicolas Cherbuin
Keyword(s):  
Blood Pressure ◽  
White Matter ◽  
Meta Analysis ◽  
Full Range ◽  
White Matter Lesions ◽  
Hippocampal Volume ◽  
Cross Sectional ◽  
Standard Deviation Increase ◽  
Brain Volumes ◽  
Dependent Relationship

Background: To summarise and quantify the evidence on the association between Blood pressure (BP), white matter lesions (WMLs), and brain volumes. Method: Electronic databases PubMed, Scopus, and Clarivate were searched in February 2020 using an established methodology and pre-determined search terms. Studies were eligible for inclusion if they reported on the association between BP and WMLs or brain volume in cognitively healthy individuals, while adjusting for age and intra-cranial volume. Results: Searches yielded 7509 articles, of which 52 (26 longitudinal and 33 cross-sectional), were eligible and had a combined sample size of 343,794 individuals. Analyses found that 93.7% of studies reported that higher BP was associated with poorer cerebral health (higher WMLs and lower brain volumes). Meta-analysis of compatible results indicated a dose-dependent relationship with every one standard deviation increase in systolic BP (SBP) above 120 mmHg being associated with a 11.2% (95% CI 2.3, 19.9, p = 0.0128) increase in WMLs and −0.13% (95% CI −0.25, −0.023, p = 0.0183) smaller hippocampal volume. Conclusion: The association between BP and brain volumes appears across the full range of BP measurements and is not limited to hypertensive individuals. Higher BP in community-residing individuals is associated with poorer cerebral health.

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