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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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, Journal Year: 2021, Volume and Issue: 18(8), P. 1484 - 1497

Published: Nov. 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.

Language: Английский

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Tau oligomer induced HMGB1 release contributes to cellular senescence and neuropathology linked to Alzheimer’s disease and frontotemporal dementia

Cell Reports, Journal Year: 2021, Volume and Issue: 36(3), P. 109419 - 109419

Published: July 1, 2021

Language: Английский

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Serum markers glial fibrillary acidic protein and neurofilament light for prognosis and monitoring in cognitively normal older people: a prospective memory clinic-based cohort study

The Lancet Healthy Longevity, Journal Year: 2021, Volume and Issue: 2(2), P. e87 - e95

Published: Jan. 19, 2021

Serum glial fibrillary acidic protein (GFAP) and neurofilament light (NfL) are putative non-amyloid blood-based biomarkers indicative of ongoing inflammatory neurodegenerative disease processes. We aimed to assess their prognostic monitoring value for progression dementia in individuals presenting at a memory clinic who cognitively normal.For this prospective cohort study, we included were normal from the Amsterdam Dementia Cohort received screening first visit annual follow-up visits. Participants without serum sample stored Biobank within 6 months baseline diagnosis after minimum excluded. measured GFAP NfL levels all participants subset participants. Using Cox proportional hazard models, investigated associations biomarker (Z-transformed) with incident (adjusted age sex), by entering markers separately then simultaneously, test independent associations. also assessed longitudinal performance on standardised neuropsychological battery covering global cognition, memory, language, executive functioning, attention age, sex, education). Finally, evaluated association slopes sex).Between July 13, 2001, Aug 17, 2016, 300 study. Mean was 61 years (SD 9), 125 (42%) women, mini-mental state examination 29 (IQR 27-29). Median time 3·0 1·9-4·2), median three visits per participant (range 2-12; 1010 total evaluations). During follow-up, 27 (9%) developed dementia. Both high (hazard ratio 3·6, 95% CI 2·2-5·7; p<0·0001) (1·8, 1·2-2·8; p=0·0037) associated increased risk When both simultaneously model, only remained an (3·3, 1·9-5·5; p<0·0001). additionally (inverted) plasma amyloid β42/40, (2·6, 1·4-5·0; p=0·0026) β42/40 (2·1, 1·2-3·6; p=0·0091) independently whereas not (1·4, 0·8-2·5; p=0·28). Linear mixed models showed that higher steeper rate decline domains attention, functioning (pfalse discovery rate<0·05), not. Repeated analyses revealed rose more steeply over compared those (p=0·0006), did (p=0·074).Our results suggest that, while seems have potential as biomarker, might be valuable predicting dementia.Alzheimer Nederland, Gieskes Strijbis Fonds.

Language: Английский

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Understanding multifactorial brain changes in type 2 diabetes: a biomarker perspective

The Lancet Neurology, Journal Year: 2020, Volume and Issue: 19(8), P. 699 - 710

Published: May 21, 2020

Language: Английский

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Plasma glial fibrillary acidic protein is raised in progranulin-associated frontotemporal dementia

Journal of Neurology Neurosurgery & Psychiatry, Journal Year: 2020, Volume and Issue: 91(3), P. 263 - 270

Published: Jan. 14, 2020

There are few validated fluid biomarkers in frontotemporal dementia (FTD). Glial fibrillary acidic protein (GFAP) is a measure of astrogliosis, known pathological process FTD, but has yet to be explored as potential biomarker.Plasma GFAP and neurofilament light chain (NfL) concentration were measured 469 individuals enrolled the Genetic FTD Initiative: 114 C9orf72 expansion carriers (74 presymptomatic, 40 symptomatic), 119 GRN mutation (88 31 53 MAPT (34 19 symptomatic) 183 non-carrier controls. Biomarker measures compared between groups using linear regression models adjusted for age sex with family membership included random effect. Participants underwent standardised clinical assessments including Mini-Mental State Examination (MMSE), Frontotemporal Lobar Degeneration-Clinical Dementia Rating scale MRI. Spearman's correlation coefficient was used investigate relationship plasma imaging measures.Plasma significantly increased symptomatic (adjusted mean difference from controls 192.3 pg/mL, 95% CI 126.5 445.6), not those expansions (9.0, -61.3 54.6), mutations (12.7, -33.3 90.4) or presymptomatic groups. positively correlated both majority disease groups, well NfL concentration. In period, higher concentrations lower cognitive score (MMSE) brain volume, while associated faster rates atrophy temporal lobe.Raised appear unique GRN-related levels potentially increasing just prior symptom onset, suggesting that may an important marker proximity helpful forthcoming therapeutic prevention trials.

Language: Английский

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GFAP as a Potential Biomarker for Alzheimer’s Disease: A Systematic Review and Meta-Analysis

Cells, Journal Year: 2023, Volume and Issue: 12(9), P. 1309 - 1309

Published: May 4, 2023

Blood biomarkers have been considered tools for the diagnosis, prognosis, and monitoring of Alzheimer’s disease (AD). Although amyloid-β peptide (Aβ) tau are primarily blood biomarkers, recent studies identified other reliable candidates that can serve as measurable indicators pathological conditions. One such candidate is glial fibrillary acidic protein (GFAP), an astrocytic cytoskeletal be detected in samples. Increasing evidence suggests GFAP levels used to detect early-stage AD. In this systematic review meta-analysis, we aimed evaluate peripheral a biomarker AD provide overview regarding its utility. Our analysis revealed level was higher Aβ-positive group than negative groups, individuals with or mild cognitive impairment (MCI) compared healthy controls. Therefore, believe clinical use measurements has potential accelerate diagnosis improve prognosis

Language: Английский

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Differential levels of plasma biomarkers of neurodegeneration in Lewy body dementia, Alzheimer’s disease, frontotemporal dementia and progressive supranuclear palsy

Journal of Neurology Neurosurgery & Psychiatry, Journal Year: 2022, Volume and Issue: 93(6), P. 651 - 658

Published: Jan. 25, 2022

This longitudinal study compared emerging plasma biomarkers for neurodegenerative disease between controls, patients with Alzheimer's (AD), Lewy body dementia (LBD), frontotemporal (FTD) and progressive supranuclear palsy (PSP).

Language: Английский

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Blood-based biomarkers for Alzheimer’s disease: Current state and future use in a transformed global healthcare landscape

Neuron, Journal Year: 2023, Volume and Issue: 111(18), P. 2781 - 2799

Published: June 8, 2023

Language: Английский

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Plasma biomarkers and genetics in the diagnosis and prediction of Alzheimer’s disease

Brain, Journal Year: 2022, Volume and Issue: 146(2), P. 690 - 699

Published: April 6, 2022

Plasma biomarkers for Alzheimer's disease-related pathologies have undergone rapid developments during the past few years, and there are now well-validated blood tests amyloid tau pathology, as well neurodegeneration astrocytic activation. To define disease with rather than clinical assessment, we assessed prediction of research-diagnosed status using these tested genetic variants associated that may reflect more accurately risk biochemically defined instead dementia. In a cohort cases [n = 1439, mean age 68 years (standard deviation 8.2)] screened controls 508, 82 6.8)], measured plasma concentrations 40 42 amino acid-long amyloid-β (Aβ) fragments (Aβ40 Aβ42, respectively), phosphorylated at acid 181 (P-tau181), neurofilament light (NfL) glial fibrillary acidic protein (GFAP) state-of-the-art Single molecule array (Simoa) technology. We relationships between risk, onset duration. also conducted genome-wide association study genes biomarkers. The accuracy diagnosis by combination all biomarkers, APOE polygenic score reached area under receiver operating characteristic curve (AUC) 0.81, most significant contributors being ε4, Aβ40 or GFAP NfL. All were significantly in (P < 4.3 × 10-5). Concentrations Aβ-related lower compared controls, whereas other biomarker levels higher cases. case-control analyses, APOE-ε4 was 0.011-4.78 10-8), except No novel single nucleotide polymorphisms found design; however, case-only analysis, two independent associations Aβ42/Aβ40 ratio WWOX COPG2 genes. Disease modelling indicates variance attributed to P-tau181 is mostly captured APOE-ε4, Aβ40, NfL explain additional variation over above APOE. identified plausible genome wide-significant sample which 50 times smaller current studies disease.

Language: Английский

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