A multicentre validation study of the diagnostic value of plasma neurofilament light

Nature Communications, Год журнала: 2021, Номер 12(1)

Опубликована: Июнь 7, 2021

Increased cerebrospinal fluid neurofilament light (NfL) is a recognized biomarker for neurodegeneration that can also be assessed in blood. Here, we investigate plasma NfL as marker of 13 neurodegenerative disorders, Down syndrome, depression and cognitively unimpaired controls from two multicenter cohorts: King's College London (n = 805) the Swedish BioFINDER study 1,464). Plasma was significantly increased all cortical amyotrophic lateral sclerosis atypical parkinsonian disorders. We demonstrate clinically useful identifying disorders patients with parkinsonism, dementia individuals among psychiatric frontotemporal cognitive impairment. Data-driven cut-offs highlighted fundamental importance age-related clinical younger age onset. Finally, performs best when applied to indicate no underlying neurodegeneration, low false positives, cut-offs.

Язык: Английский

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Differences Between Plasma and Cerebrospinal Fluid Glial Fibrillary Acidic Protein Levels Across the Alzheimer Disease Continuum

JAMA Neurology, Год журнала: 2021, Номер 78(12), С. 1471 - 1471

Опубликована: Окт. 20, 2021

Glial fibrillary acidic protein (GFAP) is a marker of reactive astrogliosis that increases in the cerebrospinal fluid (CSF) and blood individuals with Alzheimer disease (AD). However, it not known whether there are differences GFAP levels across entire AD continuum its performance similar to CSF GFAP.To evaluate plasma throughout continuum, from preclinical dementia, compared GFAP.This observational, cross-sectional study collected data July 29, 2014, January 31, 2020, 3 centers. The Translational Biomarkers Aging Dementia (TRIAD) cohort (Montreal, Canada) included continuum. Results were confirmed Alzheimer's Families (ALFA+) (Barcelona, Spain), which AD, BioCogBank Paris Lariboisière (Paris, France), symptomatic AD.Plasma measured Simoa assay main outcome. Other measurements amyloid-β 42/40 (Aβ42/40), phosphorylated tau181 (p-tau181), neurofilament light (NfL), Chitinase-3-like 1 (YKL40), soluble triggering receptor expressed on myeloid cells 2 (sTREM2) p-tau181 NfL. amyloid positron emission tomography (PET) available TRIAD ALFA+, results tau PET TRIAD.A total 300 participants (177 women [59.0%]; mean [SD] age, 64.6 [17.6] years), 384 ALFA+ (234 [60.9%]; 61.1 [4.7] 187 (116 [62.0%]; 69.9 [9.2] years) included. Plasma significantly higher comparison cognitively unimpaired (CU) Aβ-negative (TRIAD: [SD], 185.1 [93.5] pg/mL, Aβ-positive 285.0 [142.6] pg/mL; ALFA+: 121.9 [42.4] 169.9 [78.5] pg/mL). also among stages CU mild cognitive impairment [MCI] 332.5 [153.6] 388.1 [152.8] pg/mL vs Paris: MCI Aβ-positive, 368.6 [158.5] 376.4 [179.6] 161.2 [67.1] magnitude changes consistently than those GFAP. more accurately discriminated (area under curve for GFAP, 0.69-0.86; area 0.59-0.76). Moreover, positively associated pathology only concomitant Aβ pathology.This suggests sensitive biomarker detecting tracking even early AD.

Язык: Английский

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The Alzheimer's Association appropriate use recommendations for blood biomarkers in Alzheimer's disease

Alzheimer s & Dementia, Год журнала: 2022, Номер 18(12), С. 2669 - 2686

Опубликована: Июль 31, 2022

Abstract Blood‐based markers (BBMs) have recently shown promise to revolutionize the diagnostic and prognostic work‐up of Alzheimer's disease (AD), as well improve design interventional trials. Here we discuss in detail further research needed be performed before widespread use BBMs. We already now recommend BBMs (pre‐)screeners identify individuals likely AD pathological changes for inclusion trials evaluating disease‐modifying therapies, provided status is confirmed with positron emission tomography (PET) or cerebrospinal fluid (CSF) testing. also encourage studying longitudinal BBM ongoing future However, should not yet used primary endpoints pivotal Further, cautiously start using specialized memory clinics part patients cognitive symptoms results whenever possible CSF PET. Additional data are stand‐alone markers, considering care.

Язык: Английский

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Blood-based biomarkers for Alzheimer's disease: towards clinical implementation

The Lancet Neurology, Год журнала: 2021, Номер 21(1), С. 66 - 77

Опубликована: Ноя. 25, 2021

Язык: Английский

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Head-to-head comparison of 10 plasma phospho-tau assays in prodromal Alzheimer’s disease

Brain, Год журнала: 2022, Номер 146(4), С. 1592 - 1601

Опубликована: Сен. 10, 2022

Plasma phospho-tau (p-tau) species have emerged as the most promising blood-based biomarkers of Alzheimer's disease. Here, we performed a head-to-head comparison p-tau181, p-tau217 and p-tau231 measured using 10 assays to detect abnormal brain amyloid-β (Aβ) status predict future progression dementia. The study included 135 patients with baseline diagnosis mild cognitive impairment (mean age 72.4 years; 60.7% women) who were followed for an average 4.9 years. Seventy-one participants had Aβ-status (i.e. CSF Aβ42/40) at baseline; 45 these Aβ-positive progressed dementia during follow-up. P-tau concentrations determined in plasma CSF. P-tau217 p-tau181 both immunoassays developed by Lilly Research Laboratories (Lilly) mass spectrometry Washington University (WashU). was also analysed Simoa immunoassay Janssen Development (Janss). P-tau181 from ADxNeurosciences (ADx), Lumipulse Fujirebio (Fuji) Splex Mesoscale Discovery (Splex). Both quantified Gothenburg (UGOT). We found that spectrometry-based (p-tau217WashU) exhibited significantly better performance than all other p-tau when detecting Aβ [area under curve (AUC) = 0.947; Pdiff < 0.015] or (AUC 0.932; 0.027). Among immunoassays, p-tau217Lilly highest AUCs (0.886-0.889), which not different p-tau217Janss, p-tau181ADx p-tau181WashU (AUCrange 0.835-0.872; > 0.09), but higher compared AUC p-tau231UGOT, p-tau181Lilly, p-tau181UGOT, p-tau181Fuji p-tau181Splex 0.642-0.813; ≤ 0.029). Correlations between values strongest p-tau217WashU (R 0.891) 0.755; 0.003 versus p-tau217WashU) weak moderate rest (Rrange 0.320-0.669). In conclusion, our findings suggest among tested assays, measures perform best identifying those will subsequently progress Several (p-tau217Lilly, p-tau181WashU) showed relatively high consistent accuracy across outcomes. results further indicate performing metrics rival gold standards Aβ-PET If validated, significant impacts diagnosis, screening treatment future.

Язык: Английский

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Tau biomarkers in Alzheimer's disease: towards implementation in clinical practice and trials

The Lancet Neurology, Год журнала: 2022, Номер 21(8), С. 726 - 734

Опубликована: Май 25, 2022

Язык: Английский

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Differential roles of Aβ42/40, p-tau231 and p-tau217 for Alzheimer’s trial selection and disease monitoring

Nature Medicine, Год журнала: 2022, Номер 28(12), С. 2555 - 2562

Опубликована: Дек. 1, 2022

Abstract Blood biomarkers indicative of Alzheimer’s disease (AD) pathology are altered in both preclinical and symptomatic stages the disease. Distinctive may be optimal for identification AD or monitoring progression. that correlate with changes cognition atrophy during course could used clinical trials to identify successful interventions thereby accelerate development efficient therapies. When disease-modifying treatments become approved use, blood-based might also inform on treatment implementation management practice. In BioFINDER-1 cohort, plasma phosphorylated (p)-tau231 amyloid-β42/40 ratio were more changed at lower thresholds amyloid pathology. Longitudinally, however, only p-tau217 demonstrated marked amyloid-dependent over 4–6 years disease, no such observed p-tau231, p-tau181, amyloid-β42/40, glial acidic fibrillary protein neurofilament light. Only longitudinal increases associated deterioration brain AD. The selective increase its associations cognitive decline was confirmed an independent cohort (Wisconsin Registry Prevention). These findings support differential association strongly highlight as a surrogate marker progression prodromal AD, impact new treatments.

Язык: Английский

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Diagnostic Accuracy of a Plasma Phosphorylated Tau 217 Immunoassay for Alzheimer Disease Pathology

JAMA Neurology, Год журнала: 2024, Номер 81(3), С. 255 - 255

Опубликована: Янв. 22, 2024

Importance Phosphorylated tau (p-tau) is a specific blood biomarker for Alzheimer disease (AD) pathology, with p-tau217 considered to have the most utility. However, availability of tests research and clinical use has been limited. Expanding access this highly accurate AD crucial wider evaluation implementation tests. Objective To determine utility novel commercially available immunoassay plasma detect pathology evaluate reference ranges abnormal amyloid β (Aβ) longitudinal change across 3 selected cohorts. Design, Setting, Participants This cohort study examined data from single-center observational cohorts: cross-sectional Translational Biomarkers in Aging Dementia (TRIAD) (visits October 2017–August 2021) Wisconsin Registry Alzheimer’s Prevention (WRAP) February 2007–November 2020) Sant Pau Initiative on Neurodegeneration (SPIN) (baseline visits March 2009–November 2021). included individuals without cognitive impairment grouped by (AT) status using PET or CSF biomarkers. Data were analyzed June 2023. Exposures Magnetic resonance imaging, Aβ positron emission tomography (PET), PET, cerebrospinal fluid (CSF) biomarkers (Aβ42/40 p-tau immunoassays), (ALZpath pTau217 assay). Main Outcomes Measures Accuracy detecting according baseline status. Results The 786 participants (mean [SD] age, 66.3 [9.7] years; 504 females [64.1%] 282 males [35.9%]). High accuracy was observed identifying elevated (area under curve [AUC], 0.92-0.96; 95% CI, 0.89-0.99) (AUC, 0.93-0.97; 0.84-0.99) all These accuracies comparable determining signal. detection 3-range yielded reproducible results reduced confirmatory testing approximately 80%. Longitudinally, values showed an annual increase only Aβ-positive individuals, highest those positivity. Conclusions Relevance found that accurately identified biological AD, biomarkers, cut-offs It detected changes, including at preclinical stage.

Язык: Английский

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Plasma p-tau231 and p-tau217 as state markers of amyloid-β pathology in preclinical Alzheimer’s disease

Nature Medicine, Год журнала: 2022, Номер unknown

Опубликована: Авг. 11, 2022

Abstract Blood biomarkers indicating elevated amyloid-β (Aβ) pathology in preclinical Alzheimer’s disease are needed to facilitate the initial screening process of participants disease-modifying trials. Previous biofluid data suggest that phosphorylated tau231 (p-tau231) could indicate incipient Aβ pathology, but a comprehensive comparison with other putative blood is lacking. In ALFA+ cohort, all tested plasma (p-tau181, p-tau217, p-tau231, GFAP, NfL and Aβ42/40) were significantly changed disease. However, p-tau231 reached abnormal levels lowest burden. Plasma p-tau217 had strongest association positron emission tomography (PET) retention early accumulating regions associated longitudinal increases PET uptake individuals without overt at baseline. summary, better capture earliest cerebral changes, before plaque present, promising enrich population for clinical

Язык: Английский

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Developing the ATX(N) classification for use across the Alzheimer disease continuum

Nature Reviews Neurology, Год журнала: 2021, Номер 17(9), С. 580 - 589

Опубликована: Июль 8, 2021

Язык: Английский

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