Blood GFAP as an emerging biomarker in brain and spinal cord disorders

Nature Reviews Neurology, Journal Year: 2022, Volume and Issue: 18(3), P. 158 - 172

Published: Feb. 3, 2022

Language: Английский

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

JAMA Neurology, Journal Year: 2021, Volume and Issue: 78(12), P. 1471 - 1471

Published: Oct. 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.

Language: Английский

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

The Lancet Neurology, Journal Year: 2021, Volume and Issue: 21(1), P. 66 - 77

Published: Nov. 25, 2021

Language: Английский

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Plasma GFAP is an early marker of amyloid-β but not tau pathology in Alzheimer’s disease

Brain, Journal Year: 2021, Volume and Issue: 144(11), P. 3505 - 3516

Published: July 2, 2021

Abstract Although recent clinical trials targeting amyloid-β in Alzheimer’s disease have shown promising results, there is increasing evidence suggesting that understanding alternative pathways interact with metabolism and amyloid pathology might be important to halt the deterioration. In particular, supporting a critical role of astroglial activation astrocytosis disease. However, so far, no studies assessed whether independently related either or tau vivo. To address this question, we determined levels astrocytic marker GFAP plasma CSF 217 amyloid-β-negative cognitively unimpaired individuals, 71 amyloid-β-positive 78 impaired 63 individuals 75 patients non-Alzheimer’s neurodegenerative disorder from Swedish BioFINDER-2 study. Participants underwent longitudinal (18F-flutemetamol) (18F-RO948) PET as well cognitive testing. We found concentration was significantly increased all groups compared participants without (P < 0.01). addition, were significant associations between higher amyloid-β-PET signal groups, but also normal values 0.001), which remained after controlling for tau-PET signal. Furthermore, could predict positivity an area under curve 0.76, greater than performance achieved by (0.69) other glial markers (CSF YKL-40: 0.64, soluble TREM2: 0.71). correlations observed GFAP, these longer amyloid-β-PET. contrast 0.05) correlated only = 0.005). Finally, associated both decline, mediated effect on burden, secondary aggregation promote accumulation. Altogether, findings indicate early brain not aggregation, even status. This suggests should incorporated current hypothetical models pathogenesis used non-invasive accessible tool detect pathology.

Language: Английский

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Plasma glial fibrillary acidic protein is elevated in cognitively normal older adults at risk of Alzheimer’s disease

Translational Psychiatry, Journal Year: 2021, Volume and Issue: 11(1)

Published: Jan. 11, 2021

Abstract Glial fibrillary acidic protein (GFAP), an astrocytic cytoskeletal protein, can be measured in blood samples, and has been associated with Alzheimer’s disease (AD). However, plasma GFAP not investigated cognitively normal older adults at risk of AD, based on brain amyloid-β (Aβ) load. Cross-sectional analyses were carried out for Aβ1–42/Aβ1–40 ratio, a blood-based marker Aβ load, participants (65–90 years) categorised into low (Aβ−, n = 63) high (Aβ+, 33) load groups via positron emission tomography. Plasma GFAP, Aβ1–42, Aβ1–40 using the Single molecule array (Simoa) platform. levels significantly higher ( p < 0.00001), ratios lower 0.005), Aβ+ compared to Aβ− participants, adjusted covariates age, sex, apolipoprotein E-ε4 carriage. A receiver operating characteristic curve logistic regression same covariates, base model, distinguished from (area under curve, AUC 0.78), but was outperformed when added model (AUC 0.91) further improved ratio 0.92). The current findings demonstrate that are elevated AD. These observations suggest damage or activation begins pre-symptomatic stage AD is Observations present study highlight potential contribute diagnostic biomarker panel (along ratios)

Language: Английский

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The diagnostic and prognostic capabilities of plasma biomarkers in Alzheimer's disease

Alzheimer s & Dementia, Journal Year: 2021, Volume and Issue: 17(7), P. 1145 - 1156

Published: Jan. 25, 2021

Abstract Introduction This study investigated the diagnostic and disease‐monitoring potential of plasma biomarkers in mild cognitive impairment (MCI) Alzheimer's disease (AD) dementia cognitively unimpaired (CU) individuals. Methods Plasma was analyzed using Simoa assays from 99 CU, 107 MCI, 103 AD participants. Results Phosphorylated‐tau181 (P‐tau181), neurofilament light, amyloid‐β (Aβ42/40), Total‐tau Glial fibrillary acidic protein were altered but P‐tau181 significantly outperformed all differentiating CU (area under curve [AUC] = 0.91). increased MCI converters compared to non‐converters. Higher associated with steeper decline gray matter loss temporal regions. Longitudinal change strongly full sample Aβ measures Discussion detected at stages loss. These findings highlight value as a non‐invasive cost‐effective prognostic biomarker AD.

Language: Английский

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Blood‐based biomarkers for Alzheimer's disease

EMBO Molecular Medicine, Journal Year: 2021, Volume and Issue: 14(1)

Published: Dec. 3, 2021

Language: Английский

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Plasma glial fibrillary acidic protein detects Alzheimer pathology and predicts future conversion to Alzheimer dementia in patients with mild cognitive impairment

Alzheimer s Research & Therapy, Journal Year: 2021, Volume and Issue: 13(1)

Published: March 27, 2021

Plasma glial fibrillary acidic protein (GFAP) is a marker of astroglial activation and astrocytosis. We assessed the ability plasma GFAP to detect Alzheimer's disease (AD) pathology in form AD-related amyloid-β (Aβ) conversion AD dementia mild cognitive impairment (MCI) cohort.

Language: 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, Journal Year: 2020, Volume and Issue: 12(1)

Published: Sept. 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.

Language: Английский

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

Nature Reviews Neurology, Journal Year: 2020, Volume and Issue: 16(5), P. 265 - 284

Published: April 22, 2020

Language: Английский

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