scholarly journals Neurofilament light as a blood biomarker for neurodegeneration in Down syndrome

2018 ◽  
Author(s):  
Andre Strydom ◽  
Amanda Heslegrave ◽  
Carla M Startin ◽  
Kin Y Mok ◽  
John Hardy ◽  
...  
Keyword(s):  
Down Syndrome ◽  
Research Area ◽  
Blood Biomarkers ◽  
Cross Sectional ◽  
Future Directions ◽  
Neurofilament Light ◽  
Blood Biomarker ◽  
Potential Biomarker ◽  
Future Work ◽  
Genetic Form

AbstractINTRODUCTIONDown syndrome (DS) may be considered a genetic form of Alzheimer’s disease (AD) due to universal development of AD neuropathology, but diagnosis and treatment trials are hampered by a lack of reliable blood biomarkers. A potential biomarker is neurofilament light (NF-L), due to its association with axonal damage in neurodegenerative conditions.METHODSWe measured blood NF-L concentration in 100 adults with DS using Simoa NF-light® assays, and examined relationships with age, and cross-sectional and longitudinal dementia diagnosis.RESULTSNF-L levels increased with age (Spearman’s rho = 0.789, p<0.001), with a steep increase after age 40, and were predictive of dementia status (p=0.022 adjusting for age, sex, and APOE4) but showed no relationship with longstanding epilepsy or premorbid ability. Baseline NF-L levels were associated with longitudinal dementia status.DISCUSSIONNF-L is a biomarker for neurodegeneration in DS, with potential for use in future clinical trials to prevent or delay dementia.Research in contextSystematic reviewThe authors reviewed the literature using PubMed searches supplemented with our knowledge of pending papers in this research area. While blood NF-L has been associated with clinical features of progression in a number of neurodegenerative conditions, we have not identified any reports of NF-L associated with cognitive decline in DS, a genetic form of AD.InterpretationOur findings demonstrate the potential utility of NF-L as a blood biomarker of neurodegeneration in DS, a population that may not be able to tolerate more invasive procedures such as neuroimaging and lumbar punctures to track progression.Future directionsThe association between NF-L and other markers of longitudinal AD progression should be explored further in future work.

scholarly journals Cross-Sectional Exploration of Plasma Biomarkers of Alzheimer’s Disease in Down Syndrome: Early Data from the Longitudinal Investigation for Enhancing Down Syndrome Research (LIFE-DSR) Study

2021 ◽  
Vol 10 (9) ◽  
pp. 1907
Author(s):  
James A. Hendrix ◽  
David C. Airey ◽  
Angela Britton ◽  
Anna D. Burke ◽  
George T. Capone ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Down Syndrome ◽  
Amyloid Β ◽  
Neurofilament Light Chain ◽  
Cross Sectional ◽  
Neurofilament Light ◽  
Plasma Biomarkers ◽  
Show Evidence ◽  
Biomarker Data

With improved healthcare, the Down syndrome (DS) population is both growing and aging rapidly. However, with longevity comes a very high risk of Alzheimer’s disease (AD). The LIFE-DSR study (NCT04149197) is a longitudinal natural history study recruiting 270 adults with DS over the age of 25. The study is designed to characterize trajectories of change in DS-associated AD (DS-AD). The current study reports its cross-sectional analysis of the first 90 subjects enrolled. Plasma biomarkers phosphorylated tau protein (p-tau), neurofilament light chain (NfL), amyloid β peptides (Aβ1-40, Aβ1-42), and glial fibrillary acidic protein (GFAP) were undertaken with previously published methods. The clinical data from the baseline visit include demographics as well as the cognitive measures under the Severe Impairment Battery (SIB) and Down Syndrome Mental Status Examination (DS-MSE). Biomarker distributions are described with strong statistical associations observed with participant age. The biomarker data contributes to understanding DS-AD across the spectrum of disease. Collectively, the biomarker data show evidence of DS-AD progression beginning at approximately 40 years of age. Exploring these data across the full LIFE-DSR longitudinal study population will be an important resource in understanding the onset, progression, and clinical profiles of DS-AD pathophysiology.

scholarly journals Blood biomarkers for mild traumatic brain injury: a selective review of unresolved issues

2021 ◽  
Vol 9 (1) ◽  
Author(s):  
Daniel B. Hier ◽  
Tayo Obafemi-Ajayi ◽  
Matthew S. Thimgan ◽  
Gayla R. Olbricht ◽  
Sima Azizi ◽  
...  
Keyword(s):  
Traumatic Brain Injury ◽  
Brain Injury ◽  
Ct Scan ◽  
Mild Traumatic Brain Injury ◽  
Current Knowledge ◽  
Blood Biomarkers ◽  
Predictive Capacity ◽  
Neurofilament Light Chain ◽  
Neurofilament Light ◽  
Blood Biomarker

Abstract Background The use of blood biomarkers after mild traumatic brain injury (mTBI) has been widely studied. We have identified eight unresolved issues related to the use of five commonly investigated blood biomarkers: neurofilament light chain, ubiquitin carboxy-terminal hydrolase-L1, tau, S100B, and glial acidic fibrillary protein. We conducted a focused literature review of unresolved issues in three areas: mode of entry into and exit from the blood, kinetics of blood biomarkers in the blood, and predictive capacity of the blood biomarkers after mTBI. Findings Although a disruption of the blood brain barrier has been demonstrated in mild and severe traumatic brain injury, biomarkers can enter the blood through pathways that do not require a breach in this barrier. A definitive accounting for the pathways that biomarkers follow from the brain to the blood after mTBI has not been performed. Although preliminary investigations of blood biomarkers kinetics after TBI are available, our current knowledge is incomplete and definitive studies are needed. Optimal sampling times for biomarkers after mTBI have not been established. Kinetic models of blood biomarkers can be informative, but more precise estimates of kinetic parameters are needed. Confounding factors for blood biomarker levels have been identified, but corrections for these factors are not routinely made. Little evidence has emerged to date to suggest that blood biomarker levels correlate with clinical measures of mTBI severity. The significance of elevated biomarker levels thirty or more days following mTBI is uncertain. Blood biomarkers have shown a modest but not definitive ability to distinguish concussed from non-concussed subjects, to detect sub-concussive hits to the head, and to predict recovery from mTBI. Blood biomarkers have performed best at distinguishing CT scan positive from CT scan negative subjects after mTBI.

scholarly journals NFL strongly correlates with TNF-R1 in the plasma of AD patients, but not with cognitive decline

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Constance Delaby ◽  
A. Julian ◽  
G. Page ◽  
S. Ragot ◽  
Sylvain Lehmann ◽  
...  
Keyword(s):  
Cognitive Decline ◽  
Patient Care ◽  
Strong Correlation ◽  
Peripheral Inflammation ◽  
Blood Biomarkers ◽  
Neurofilament Light ◽  
Blood Biomarker ◽  
Potential Association ◽  
First Time

AbstractPeripheral inflammation mechanisms involved in Alzheimer's disease (AD) have yet to be accurately characterized and the identification of blood biomarker profiles could help predict cognitive decline and optimize patient care. Blood biomarkers described to date have failed to provide a consensus signature, which is mainly due to the heterogeneity of the methods used or the cohort. The present work aims to describe the potential informativity of peripheral inflammation in AD, focusing in particular on the potential association between the level of plasma neurofilament light (NFL), peripheral inflammation (by quantifying IL-1β, IL-6, TNFα, CCL5, TNF-R1, sIL-6R, TIMP-1, IL-8 in blood) and cognitive decline (assessed by the MMSE and ADAScog scales) through a 2-year follow-up of 40 AD patients from the Cytocogma cohort (CHU Poitiers, Pr M. Paccalin). Our results show for the first time a strong correlation between plasma NFL and TNF-R1 at each time of follow-up (baseline, 12 and 24 months), thus opening an interesting perspective for the prognosis of AD patients.

scholarly journals Neurofilament light as a blood biomarker for neurodegeneration in Down syndrome

2018 ◽  
Vol 10 (1) ◽  
Author(s):  
Andre Strydom ◽  
◽  
Amanda Heslegrave ◽  
Carla M. Startin ◽  
Kin Y. Mok ◽  
...  
Keyword(s):  
Down Syndrome ◽  
Neurofilament Light ◽  
Blood Biomarker

scholarly journals Blood Biomarkers for Alzheimer’s Disease in Down Syndrome

2021 ◽  
Vol 10 (16) ◽  
pp. 3639
Author(s):  
Laia Montoliu-Gaya ◽  
Andre Strydom ◽  
Kaj Blennow ◽  
Henrik Zetterberg ◽  
Nicholas James Ashton
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Down Syndrome ◽  
Amyloid Β ◽  
Detection Methods ◽  
Blood Biomarkers ◽  
Neurofilament Light Chain ◽  
Neurofilament Light ◽  
Positron Emission ◽  
Diagnosis Of Dementia

Epidemiological evidence suggests that by the age of 40 years, all individuals with Down syndrome (DS) have Alzheimer’s disease (AD) neuropathology. Clinical diagnosis of dementia by cognitive assessment is complex in these patients due to the pre-existing and varying intellectual disability, which may mask subtle declines in cognitive functioning. Cerebrospinal fluid (CSF) and positron emission tomography (PET) biomarkers, although accurate, are expensive, invasive, and particularly challenging in such a vulnerable population. The advances in ultra-sensitive detection methods have highlighted blood biomarkers as a valuable and realistic tool for AD diagnosis. Studies with DS patients have proven the potential blood-based biomarkers for sporadic AD (amyloid-β, tau, phosphorylated tau, and neurofilament light chain) to be useful in this population. In addition, biomarkers related to other pathologies that could aggravate dementia progression—such as inflammatory dysregulation, energetic imbalance, or oxidative stress—have been explored. This review serves to provide a brief overview of the main findings from the limited neuroimaging and CSF studies, outline the current state of blood biomarkers to diagnose AD in patients with DS, discuss possible past limitations of the research, and suggest considerations for developing and validating blood-based biomarkers in the future.

scholarly journals The Association between Difficulties with Speech Fluency and Language Skills in a National Age Cohort of Children with Down Syndrome

2021 ◽  
Vol 11 (6) ◽  
pp. 704
Author(s):  
Kari-Anne B. Næss ◽  
Egil Nygaard ◽  
Hilde Hofslundsengen ◽  
J. Scott Yaruss
Keyword(s):  
Down Syndrome ◽  
Language Skills ◽  
Typically Developing ◽  
Typically Developing Children ◽  
Cross Sectional ◽  
Exact Test ◽  
Children With Down Syndrome ◽  
Speech Fluency ◽  
Age Cohort ◽  
Student’S T

The present study (a) addressed difficulties in speech fluency in children with Down syndrome and typically developing children at a similar non-verbal level and (b) examined the association between difficulties with speech fluency and language skills in children with Down syndrome. Data from a cross-sectional parent survey that included questions about children’s difficulties with speech fluency, as well as clinical tests from a national age cohort of 43 six-year-olds with Down syndrome and 57 young typically developing children, were collected. Fisher’s exact test, Student’s t-test, linear regression, and density ellipse scatter plots were used for analysis. There was a significantly higher occurrence of parent-reported difficulties with speech fluency in the children with Down syndrome. Higher language scores were significantly associated with a lower degree of difficulties; this association was strongest for vocabulary and phonological skills. Although difficulties with speech fluency were not reported for all children with Down syndrome, a substantially higher occurrence of such difficulties was reported compared to that for typically developing children. The significant association between difficulties with speech fluency and the level of language functioning suggests that speech fluency and language skills should be taken into consideration when planning treatment for children with Down syndrome.

scholarly journals SAT0415 AGE RELATIONSHIP WITH ULTRASOUND ARTICULAR AND ENTHESEAL INVOLVEMENT IN PSORIATIC ARTHRITIS: CROSS-SECTIONAL STUDY

2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 1160.2-1161
Author(s):  
I. Fairushina ◽  
D. Abdulganieva ◽  
E. Kirillova ◽  
R. Abdrakipov
Keyword(s):  
Psoriatic Arthritis ◽  
Disease Activity ◽  
Power Doppler ◽  
Severity Index ◽  
Cross Sectional Study ◽  
Blood Biomarkers ◽  
Cross Sectional ◽  
Age Related ◽  
Hs Crp ◽  
Axial Involvement

Background:Detection of subclinical enthesitis and synovitis in psoriatic arthritis (PsA) is prevalent and ultrasound (US) examination is informative tool for it diagnosing. Aging positively affects degenerative changes.Objectives:To study relationship between US articular and entheseal findings with age in patients with PsA.Methods:57 patients were enrolled to study with fulfilled PsA criteria (CASPAR, 2009). Data collection: demographical, clinical (current psoriasis, axial involvement, enthesitis, dactylitis), US (synovitis count (by Grey Scale), Power Doppler(PD)+ synovitis), thickening and hypoechogenicity at enthesis, PD+ enthesitis, entheses with structural components); biological (high sensitive C-reactive protein (hsCRP), Erythrocyte Sedimentation Rate (ESR).US examination included 798 joints and 3078 entheses (bilateral shoulders, acromioclavicular joints, elbows, wrists, hips, knees, ankles; entheses at the projection of these joints (total number - 54). US entheseal findings were fixed according to consensus-based US definition and scoring for enthesitis in spondyloarthritis and PsA (OMERACT US)1.Results:In all 57 patients: male - 25 (43.9%), mean age 43.4±10.3(SD) years (y), PsA duration was 7 (3;10) y, Ps duration 10 (8; 22) y; 53 (41.1%) had axial involvement, 42 (73.7%) dactylitis, 8 (14%) clinical enthesitis, and 56 (98.2 %) skin psoriasis, Psoriasis Activity and Severity Index score 6.4 (2;14.4), Disease Activity in PsA score 18.1 (10.2;26.1), hsCRP 10.1(2.4;21.4), ESR 20 (11.3;31.5).Synovitis count increased with age noticeably (r=0.508, p<0.01), and weak correlation of PD+ synovitis (r=0.262, p=0.049) and age was found. The entheseal thickening and hypoechogenicity and structural findings increased with age respectively (r=0.345, p=0.009; r=0.337, p=0.01). There was no correlation between PD+ enthesitis and age. The assosiation between PD+ enthesitis and blood biomarkers of inflammation (hs-CRP (r=0.364, p=0.008); ESR (p=0.358, p=0.008) was found.Conclusion:Our study found significant relationship between age and US synovitis. Association between age and US entheseal involvement was noted. Only PD+ enthesitis was not related with age in comparison with other US entheseal findings. The presence of PD US signal at enthesitis in association with increased inflammatory blood biomarkers can be evaluated as the sign of disease activity regardless of age and not as age-related lesion in PsA patients.References:[1]Balint PV, Terslev L, Aegerter P et al. Reliability of a consensus-based ultrasound definition and scoring for enthesitis in spondyloarthritis and psoriatic arthritis: an OMERACT US initiative. Ann Rheum Dis.;2018;77(12):1730-1735.Disclosure of Interests:None declared

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.

Blood Biomarkers Relate to Cognitive Performance Years after Traumatic Brain Injury in Service Members and Veterans

2020 ◽  
pp. 1-7
Author(s):  
Sara M. Lippa ◽  
Jessica Gill ◽  
Tracey A. Brickell ◽  
Louis M. French ◽  
Rael T. Lange
Keyword(s):  
Traumatic Brain Injury ◽  
Brain Injury ◽  
Cognitive Outcome ◽  
Service Members ◽  
Neurocognitive Performance ◽  
Blood Biomarkers ◽  
Post Injury ◽  
Blood Draw ◽  
Neurofilament Light ◽  
History Of

Abstract Objective: This study examines the relationship of serum total tau, neurofilament light (NFL), ubiquitin carboxyl-terminal hydrolase L1 (UCH-L1), and glial fibrillary acidic protein (GFAP) with neurocognitive performance in service members and veterans with a history of traumatic brain injury (TBI). Method: Service members (n = 488) with a history of uncomplicated mild (n = 172), complicated mild, moderate, severe, or penetrating TBI (sTBI; n = 126), injured controls (n = 116), and non-injured controls (n = 74) prospectively enrolled from Military Treatment Facilities. Participants completed a blood draw and neuropsychological assessment a year or more post-injury. Six neuropsychological composite scores and presence/absence of mild neurocognitive disorder (MNCD) were evaluated. Within each group, stepwise hierarchical regression models were conducted. Results: Within the sTBI group, increased serum UCH-L1 was related to worse immediate memory and delayed memory (R2Δ = .065–.084, ps < .05) performance, while increased GFAP was related to worse perceptual reasoning (R2Δ = .030, p = .036). Unexpectedly, within injured controls, UCH-L1 and GFAP were inversely related to working memory (R2Δ = .052–.071, ps < .05), and NFL was related to executive functioning (R2Δ = .039, p = .021) and MNCD (Exp(B) = 1.119, p = .029). Conclusions: Results suggest GFAP and UCH-L1 could play a role in predicting poor cognitive outcome following complicated mild and more severe TBI. Further investigation of blood biomarkers and cognition is warranted.

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