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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Biomarkers for Alzheimer’s disease—preparing for a new era of disease-modifying therapies

Molecular Psychiatry, Journal Year: 2020, Volume and Issue: 26(1), P. 296 - 308

Published: April 6, 2020

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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Diagnostic and prognostic plasma biomarkers for preclinical Alzheimer's disease

Alzheimer s & Dementia, Journal Year: 2021, Volume and Issue: 18(6), P. 1141 - 1154

Published: Sept. 8, 2021

Abstract Introduction This study involved a parallel comparison of the diagnostic and longitudinal monitoring potential plasma glial fibrillary acidic protein (GFAP), total tau (t‐tau), phosphorylated (p‐tau181 p‐tau231), neurofilament light (NFL) in preclinical Alzheimer's disease (AD). Methods Plasma proteins were measured using Simoa assays cognitively unimpaired older adults (CU), with either absence (Aβ−) or presence (Aβ+) brain amyloidosis. Results GFAP, t‐tau, p‐tau181, p‐tau231 concentrations higher Aβ+ CU compared Aβ− cross‐sectionally. GFAP had highest effect size area under curve (AUC) differentiating between CU; however, no statistically significant differences observed AUCs p‐tau231, but all significantly than AUC NFL, was t‐tau. The combination base model (BM), comprising AD risk factors, age, sex, apolipoprotein E gene ( APOE ) ε4 status to have (>90%) BM any other investigated current study. Longitudinal analyses showed increased p‐tau181 NFL CU, over 12‐month duration. correlations cognition, whereas hippocampal volume. Discussion These findings highlight p‐tau for AD.

Language: Английский

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The crosstalk: exosomes and lipid metabolism

Cell Communication and Signaling, Journal Year: 2020, Volume and Issue: 18(1)

Published: Aug. 3, 2020

Abstract Exosomes have been considered as novel and potent vehicles of intercellular communication, instead “cell dust”. are consistent with anucleate cells, organelles lipid bilayer consisting the proteins abundant lipid, enhancing their “rigidity” “flexibility”. Neighboring cells or distant capable exchanging genetic metabolic information via exosomes binding to recipient cell releasing bioactive molecules, such lipids, proteins, nucleic acids. Of note, exert remarkable effects on metabolism, including synthesis, transportation degradation lipid. The disorder metabolism mediated by leads occurrence progression diseases, atherosclerosis, cancer, non-alcoholic fatty liver disease (NAFLD), obesity Alzheimer’s diseases so on. More importantly, can also affect production secretion exosomes, well interactions cells. Therefore, may be applied effective targets for diagnosis treatment diseases.

Language: Английский

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Plasma Aβ42/40 ratio, p‐tau181, GFAP, and NfL across the Alzheimer's disease continuum: A cross‐sectional and longitudinal study in the AIBL cohort

Alzheimer s & Dementia, Journal Year: 2022, Volume and Issue: 19(4), P. 1117 - 1134

Published: July 21, 2022

Plasma amyloid beta (Aβ)1-42/Aβ1-40 ratio, phosphorylated-tau181 (p-tau181), glial fibrillary acidic protein (GFAP), and neurofilament light (NfL) are putative blood biomarkers for Alzheimer's disease (AD). However, head-to-head cross-sectional longitudinal comparisons of the aforementioned across AD continuum lacking.Plasma Aβ1-42, Aβ1-40, p-tau181, GFAP, NfL were measured utilizing Single Molecule Array (Simoa) platform compared cross-sectionally continuum, wherein Aβ-PET (positron emission tomography)-negative cognitively unimpaired (CU Aβ-, n = 81) mild cognitive impairment (MCI 26) participants with Aβ-PET-positive Aβ+, 39; MCI 33; 46) from Australian Imaging, Biomarker & Lifestyle Flagship Study Ageing (AIBL) cohort. Longitudinal plasma biomarker changes also assessed in (n 27) 29) CU 120) participants. In addition, associations between baseline levels prospective decline load over a 7 to 10-year duration.Lower Aβ1-42/Aβ1-40 ratio elevated p-tau181 GFAP observed whereas was Aβ+ Aβ- Aβ-. Among biomarkers, models without risk factors (age, sex, apolipoprotein E (APOE) ε4 carrier status), performed equivalent or better than other predicting brain Aβ-/+ status continuum. factors, panel Aβ1-42/Aβ1-40, any alone Longitudinally, altered CU, CU. lower higher associated increased prospectively.These findings suggest that longitudinally, along prospectively load. although an may have superior predictive capability continuum.Area under curve (AUC) ≥ AUC Aβ42/40, PET (Aβ-/+). Aβ42/40+p-tau181+GFAP Aβ42/40/p-tau181/GFAP/NfL Aβ-/+. versus decline. Aβ prospectively.

Language: Английский

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