Serum neurofilament light levels in normal aging and their association with morphologic brain changes

Nature Communications, Год журнала: 2020, Номер 11(1)

Опубликована: Фев. 10, 2020

Abstract Neurofilament light (NfL) protein is a marker of neuro-axonal damage and can be measured not only in cerebrospinal fluid but also serum, which allows for repeated assessments. There still limited knowledge regarding the association serum NfL (sNfL) with age subclinical morphologic brain changes their dynamics normal population. We sNfL by single molecule array (Simoa) assay 335 individuals participating population-based cohort study after mean follow-up time 5.9 years (n = 103). Detailed clinical examination, cognitive testing 3T MRI were performed to assess damage. show that rising more variable >60 indicate an acceleration neuronal injury at higher age, may driven comorbid pathologies. This supported close volume cross-sectional especially longitudinal manner.

Язык: Английский

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Blood‐based biomarkers for Alzheimer's disease

EMBO Molecular Medicine, Год журнала: 2021, Номер 14(1)

Опубликована: Дек. 3, 2021

Язык: Английский

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Blood neurofilament light: a critical review of its application to neurologic disease

Annals of Clinical and Translational Neurology, Год журнала: 2020, Номер 7(12), С. 2508 - 2523

Опубликована: Ноя. 4, 2020

Abstract Neuronal injury is a universal event that occurs in disease processes affect both the central and peripheral nervous systems. A blood biomarker linked to neuronal would provide critical measure understand treat neurologic diseases. Neurofilament light chain (NfL), cytoskeletal protein expressed only neurons, has emerged as such biomarker. With ability quantify damage blood, NfL being applied wide range of conditions investigate monitor including assessment treatment efficacy. Blood not specific for one its release can also be induced by physiological processes. Longitudinal studies multiple sclerosis, traumatic brain injury, stroke show accumulation over days followed elevated levels months. Therefore, it may hard determine with single measurement when peak reached are normalized. Nonetheless, provides new diseases overcoming invasiveness CSF sampling restricted clinical application. In this review, we examine use biologic test disease.

Язык: Английский

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

Frontiers in Neuroscience, Год журнала: 2021, Номер 15

Опубликована: Сен. 27, 2021

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

Язык: Английский

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Combination of plasma amyloid beta(1-42/1-40) and glial fibrillary acidic protein strongly associates with cerebral amyloid pathology

Alzheimer s Research & Therapy, Год журнала: 2020, Номер 12(1)

Опубликована: Сен. 28, 2020

Abstract Background Blood-based biomarkers for Alzheimer’s disease (AD) might facilitate identification of participants clinical trials targeting amyloid beta (Abeta) accumulation, and aid in AD diagnostics. We examined the potential plasma markers Abeta (1-42/1-40) , glial fibrillary acidic protein (GFAP) neurofilament light (NfL) to identify cerebral amyloidosis and/or severity. Methods included individuals with a positive ( n = 176: 63 ± 7 years, 87 (49%) females) or negative 76: 61 9 27 (36%) PET status, syndrome diagnosis subjective cognitive decline (18 PET+, 25 PET−), mild impairment (26 24 AD-dementia (132 PET+). Plasma GFAP, NfL were measured by Simoa. applied two-way ANOVA adjusted age sex investigate associations status diagnosis; logistic regression analysis Wald’s backward selection an optimal panel that identifies positivity; age, sex, education-adjusted linear between neuropsychological test performance; Spearman’s correlation medial temporal lobe atrophy (MTA). Results GFAP independently associated p 0.009 < 0.001 respectively), 0.048 respectively). The identifying alongside APOE (AUC 88% (95% CI 83–93%), 82% sensitivity, 86% specificity), while excluding sex. robustly performance on global cognition all major domains (GFAP: range standardized β (sβ) − 0.40 0.26; NfL: sβ 0.35 0.18; all: 0.002), whereas cognition, memory, attention, executive functioning (range 0.22 – 0.11; 0.05) but not language. showed moderate correlations MTA (both: rho> 0.33, 0.001). (Spearman’s rho 0.24, Discussion conclusions Combination provides valuable tool status. Furthermore, associate various severity measures suggesting monitoring.

Язык: Английский

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Early diagnosis of Alzheimer’s disease: the role of biomarkers including advanced EEG signal analysis. Report from the IFCN-sponsored panel of experts

Clinical Neurophysiology, Год журнала: 2020, Номер 131(6), С. 1287 - 1310

Опубликована: Март 12, 2020

Язык: Английский

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Associations of amyloid and neurodegeneration plasma biomarkers with comorbidities

Alzheimer s & Dementia, Год журнала: 2021, Номер 18(6), С. 1128 - 1140

Опубликована: Сен. 27, 2021

Blood-based biomarkers of amyloid pathology and neurodegeneration are entering clinical use. It is critical to understand what factors affect the levels these markers.

Язык: Английский

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An update on blood-based biomarkers for non-Alzheimer neurodegenerative disorders

Nature Reviews Neurology, Год журнала: 2020, Номер 16(5), С. 265 - 284

Опубликована: Апрель 22, 2020

Язык: Английский

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Characterization of pre‐analytical sample handling effects on a panel of Alzheimer's disease–related blood‐based biomarkers: Results from the Standardization of Alzheimer's Blood Biomarkers (SABB) working group

Alzheimer s & Dementia, Год журнала: 2021, Номер 18(8), С. 1484 - 1497

Опубликована: Ноя. 29, 2021

Pre-analytical sample handling might affect the results of Alzheimer's disease blood-based biomarkers. We empirically tested variations common blood collection and procedures.We created sets that address effect tube type, ethylene diamine tetraacetic acid plasma delayed centrifugation, centrifugation temperature, aliquot volume, storage, freeze-thawing. measured amyloid beta (Aβ)42 40 peptides with six assays, Aβ oligomerization-tendency (OAβ), precursor protein (APP)699-711 , glial fibrillary acidic (GFAP), neurofilament light (NfL), total tau (t-tau), phosphorylated tau181.Collection type resulted in different values all assessed markers. Delayed storage affected t-tau; t-tau was additionally by temperature. The other markers were resistant to variations.We constructed a standardized operating procedure for handling, facilitate introduction biomarkers into research clinical settings.

Язык: Английский

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Increased plasma neurofilament light chain concentration correlates with severity of post-mortem neurofibrillary tangle pathology and neurodegeneration

Acta Neuropathologica Communications, Год журнала: 2019, Номер 7(1)

Опубликована: Янв. 9, 2019

Alzheimer’s disease (AD) is pathologically characterized by the accumulation of amyloid-β (Aβ) plaques, neurofibrillary tangles and widespread neuronal loss in brain. In recent years, blood biomarkers have emerged as a realistic prospect to highlight accumulating pathology for secondary prevention trials. Neurofilament light chain (NfL), marker axonal degeneration, robustly elevated many neurological neurodegenerative conditions, including AD. A strong relationship with cerebrospinal fluid (CSF) NfL suggests that these biomarker modalities reflect same pathological process. Yet, connection between brain tissue has not been directly compared. this study, longitudinal plasma from cognitively healthy controls (n = 12) AD participants 57) were quantified Simoa platform. On reaching post-mortem, neuropathological assessment was performed on all participants, additional frozen paraffin-embedded acquired 26 further biochemical (Aβ1–42, Aβ1–40, tau) histological (NfL) evaluation. Plasma concentrations significantly increased correlated cognitive decline, independent age. Retrospective stratification based Braak staging revealed baseline associated higher tangle at post-mortem. Longitudinal increases observed groupings; significant negative association, however, found time point 1 both its rate change annual percentage increase. Immunohistochemical evaluation medial temporal gyrus (MTG) demonstrated an inverse stages staining. Importantly, correlation measurement closest death level staining MTG For first time, we demonstrate associates severity neurodegeneration post-mortem

Язык: Английский

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