Blood‐based biomarkers in Alzheimer disease: Current state of the science and a novel collaborative paradigm for advancing from discovery to clinic

Alzheimer s & Dementia, Год журнала: 2016, Номер 13(1), С. 45 - 58

Опубликована: Ноя. 18, 2016

Abstract The last decade has seen a substantial increase in research focused on the identification of blood‐based biomarkers that have utility Alzheimer's disease (AD). Blood‐based significant advantages being time‐ and cost‐efficient as well reduced invasiveness increased patient acceptance. Despite these efforts, field been hampered by lack reproducibility an unclear path for moving basic discovery toward clinical utilization. Here we reviewed recent literature AD to provide current state art. In addition, collaborative model is proposed leverages academic industry strengths facilitate past only work use. Key resources are provided. This new public‐private partnership intended circumvent traditional handoff clear useful paradigm advancement biomarker science other neurodegenerative diseases.

Язык: Английский

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Plasma neurofilament light as a potential biomarker of neurodegeneration in Alzheimer’s disease

Alzheimer s Research & Therapy, Год журнала: 2018, Номер 10(1)

Опубликована: Июль 28, 2018

A growing body of evidence suggests that the plasma concentration neurofilament light chain (NfL) might be considered a biomarker for screening neurodegeneration in Alzheimer's disease (AD). With single molecule array method (Simoa, Quanterix), NfL concentrations were measured 99 subjects with AD at stage mild cognitive impairment (MCI-AD; n = 25) or early dementia (ADD; 33), and nondemented controls (n 41); all patients, clinical diagnoses accordance results four core cerebrospinal fluid (CSF) biomarkers (amyloid β (Aβ)1–42, Aβ42/40, Tau, pTau181), interpreted according to Erlangen Score algorithm. The influence preanalytical storage procedures on was tested samples exposed six different conditions. significantly increased more than one freezing/thawing cycle, those stored 5 days room temperature 4 °C. Compared control group (22.0 ± 12.4 pg/mL), unadjusted highly higher MCI-AD (38.1 15.9 pg/mL, p < 0.005) even further elevated ADD (49.1 28.4 pg/mL; 0.001). significant association between age (ρ 0.65, 0.001) observed; after correcting age, difference remained (p 0.044). At cutoff value 25.7 unconditional sensitivity, specificity, accuracy 0.84, 0.78, 0.82, respectively. Unadjusted correlation Mini Mental State Examination (MMSE) across patients moderate but (r −0.49, We observed an overall CSF biomarkers, this not within diagnostic groups. This study confirms compared controls.

Язык: Английский

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Glial Fibrillary Acidic Protein in Serum is Increased in Alzheimer’s Disease and Correlates with Cognitive Impairment

Journal of Alzheimer s Disease, Год журнала: 2018, Номер 67(2), С. 481 - 488

Опубликована: Дек. 24, 2018

Reliable blood biomarkers for Alzheimer’s disease (AD) are missing. We measured astroglial GFAP in patients with AD ( n = 28), frontotemporal dementia (bvFTD, 35), Parkinson’s 11), Lewy body dementias 19), and controls 34). Serum was increased p < 0.001) DLB/PDD 0.01), cerebrospinal fluid all neurodegenerative diseases 0.001). correlated the Mini-Mental State Examination score r= –0.42, might be a follow-up marker clinical trials. Sensitivity specificity of serum versus bvFTD 89% 79% first biomarker differential diagnosis bvFTD.

Язык: Английский

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Cerebrospinal fluid and blood biomarkers for neurodegenerative dementias: An update of the Consensus of the Task Force on Biological Markers in Psychiatry of the World Federation of Societies of Biological Psychiatry

The World Journal of Biological Psychiatry, Год журнала: 2017, Номер 19(4), С. 244 - 328

Опубликована: Окт. 27, 2017

In the 12 years since publication of first Consensus Paper WFSBP on biomarkers neurodegenerative dementias, enormous advancement has taken place in field, and Task Force takes now opportunity to extend update original paper. New concepts Alzheimer's disease (AD) conceptual interactions between AD dementia due were developed, resulting two sets for diagnostic/research criteria. Procedures pre-analytical sample handling, biobanking, analyses post-analytical interpretation results intensively studied optimised. A global quality control project was introduced evaluate monitor inter-centre variability measurements with goal harmonisation results. Contexts use how approach candidate biological specimens other than cerebrospinal fluid (CSF), e.g. blood, precisely defined. Important development achieved neuroimaging techniques, including studies comparing amyloid-β positron emission tomography fluid-based modalities. Similarly, research laboratory technologies, such as ultra-sensitive methods, raises our hopes further improve analytical diagnostic accuracy classic novel biomarkers. Synergistically, clinical trials anti-dementia therapies energises motivates efforts find optimise most reliable early Finally, published addressing potential cost-effectiveness biomarkers-based diagnosis disorders.

Язык: Английский

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Plasma tau, neurofilament light chain and amyloid-β levels and risk of dementia; a population-based cohort study

Brain, Год журнала: 2020, Номер 143(4), С. 1220 - 1232

Опубликована: Фев. 5, 2020

CSF biomarkers, including total-tau, neurofilament light chain (NfL) and amyloid-β, are increasingly being used to define stage Alzheimer's disease. These biomarkers can be measured more quickly less invasively in plasma may provide important information for early diagnosis of We stored samples clinical data obtained from 4444 non-demented participants the Rotterdam study at baseline (between 2002 2005) during follow-up until January 2016. Plasma concentrations NfL, amyloid-β40 amyloid-β42 were using Simoa NF-light® N3PA assays. Associations between biomarker levels incident all-cause disease dementia assessed Cox proportional-hazard regression models adjusted age, sex, education, cardiovascular risk factors APOE ε4 status. Moreover, rates change over time who developed compared with age sex-matched dementia-free control subjects. During up 14 years follow-up, 549 dementia, 374 cases dementia. A log2 higher level was associated a lower developing or hazard ratio (HR) 0.61 [95% confidence interval (CI), 0.47-0.78; P < 0.0001] 0.59 (95% CI, 0.43-0.79; = 0.0006), respectively. Conversely, NfL [adjusted HR 1.59 1.38-1.83); 1.50 1.26-1.78); 0.0001]. Combining lowest quartile group highest resulted stronger association 9.5 2.3-40.4); 0.002] 15.7 2.1-117.4); 0.0001], NfL. Total-tau not risk. Trajectory analyses revealed that mean increased 3.4 times faster those remained (P 0.0001), values diverged controls 9.6 before diagnosis. Amyloid-β42 began decrease few diagnosis, although decline did reach significance participants. In conclusion, our shows low high each independently combination strongly indicate assess population. levels, specific, also useful monitoring progression

Язык: Английский

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Serum neurofilament light in familial Alzheimer disease

Neurology, Год журнала: 2017, Номер 89(21), С. 2167 - 2175

Опубликована: Окт. 26, 2017

Objectives:

To investigate whether serum neurofilament light (NfL) concentration is increased in familial Alzheimer disease (FAD), both pre and post symptom onset, it associated with markers of stage severity.

Methods:

We recruited 48 individuals from families PSEN1 or APP mutations to a cross-sectional study: 18 had symptomatic (AD) 30 were asymptomatic but at 50% risk carrying mutation. Serum NfL was measured using an ultrasensitive immunoassay on the single molecule array (Simoa) platform. Cognitive testing MRI performed; 33 participants serial MRI, allowing calculation atrophy rates. Genetic established mutation status. A generalized least squares regression model used compare among carriers, presymptomatic noncarriers, adjusting for age sex. Spearman coefficients assessed associations between (1) estimated years to/from onset (EYO), (2) cognitive measures, (3) measures atrophy.

Results:

Nineteen carriers (mean EYO −9.6); 11 noncarriers. Compared higher (p < 0.0001) = 0.007). Across all correlated (ρ 0.81, p multiple imaging including Mini-Mental State Examination −0.62, 0.0001), Clinical Dementia Rating Scale sum boxes 0.79, baseline brain volume 0.0002), whole-brain rate 0.53, 0.01).

Conclusions:

FAD prior correlates may thus be feasible biomarker early AD-related neurodegeneration.

Язык: Английский

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Neurofilament light chain in serum for the diagnosis of amyotrophic lateral sclerosis

Journal of Neurology Neurosurgery & Psychiatry, Год журнала: 2018, Номер 90(2), С. 157 - 164

Опубликована: Окт. 11, 2018

Objective To determine the diagnostic and prognostic performance of serum neurofilament light chain (NFL) in amyotrophic lateral sclerosis (ALS). Methods This single-centre, prospective, longitudinal study included following patients: 124 patients with ALS; 50 without neurodegenerative diseases; 44 conditions differential diagnosis ALS (disease controls); 65 other diseases (20 frontotemporal dementia, 20 Alzheimer’s disease, 19 Parkinson’s 6 Creutzfeldt-Jakob disease (CJD)). Serum NFL levels were measured using ultrasensitive single molecule array (Simoa) technology. Results higher comparison to all categories except for CJD. A cut-off level 62 pg/mL discriminated between 85.5% sensitivity (95% CI 78% 91.2%) 81.8% specificity 74.9% 87.4%). Among ALS, correlated positively progression rate (r s =0.336, 95% 0.14 0.506, p=0.0008), associated shorter survival (p=0.0054). did not differ among different pathological stages as evaluated by diffusion-tensor imaging, stable over time. Conclusions is increased can serve biomarker. We established a ALS.

Язык: Английский

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Levels of plasma neurofilament light chain and cognitive function in patients with Alzheimer or Parkinson disease

Scientific Reports, Год журнала: 2018, Номер 8(1)

Опубликована: Ноя. 20, 2018

Plasma neurofilament light (NFL) has been proposed as a blood-based biomarker for neurodegeneration in Alzheimer's disease (AD) and parkinsonian disorders. However, the relationship between plasma NFL cognitive decline dementia due to Parkinson's (PD) remains be elucidated. In this research, 119 AD, 56 mild impairment (MCI), 26 non-demented PD (PDND), 23 (PDD) patients, well 59 cognitively healthy controls (HC) were recruited. Each subject underwent battery of neuropsychological testing. levels measured duplicate using an NF-Light assay transferred onto Simoa platform with home-brew kit. was significantly increased AD group, compared control, MCI, PDND, PDD groups. higher PDND group. High correlated poor cognition PD, but not motor symptoms PD. may represent more specificity AD.

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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Emerging diagnostics and therapeutics for Alzheimer disease

Nature Medicine, Год журнала: 2023, Номер 29(9), С. 2187 - 2199

Опубликована: Сен. 1, 2023

Язык: Английский

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