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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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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Associations of amyloid and neurodegeneration plasma biomarkers with comorbidities

Alzheimer s & Dementia, Journal Year: 2021, Volume and Issue: 18(6), P. 1128 - 1140

Published: Sept. 27, 2021

Blood-based biomarkers of amyloid pathology and neurodegeneration are entering clinical use. It is critical to understand what factors affect the levels these markers.

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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The performance of plasma amyloid beta measurements in identifying amyloid plaques in Alzheimer’s disease: a literature review

Alzheimer s Research & Therapy, Journal Year: 2022, Volume and Issue: 14(1)

Published: Dec. 27, 2022

Abstract The extracellular buildup of amyloid beta (Aβ) plaques in the brain is a hallmark Alzheimer’s disease (AD). Detection Aβ pathology essential for AD diagnosis and identifying recruiting research participants clinical trials evaluating disease-modifying therapies. Currently, diagnoses are usually made by assessments, although detection with positron emission tomography (PET) scans or cerebrospinal fluid (CSF) analysis can be used specialty clinics. These measures aggregation, e.g. plaques, protofibrils, oligomers, medically invasive often only available at specialized medical centers not covered insurance, PET costly. Therefore, major goal recent years has been to identify blood-based biomarkers that accurately detect cost-effective, minimally procedures. To assess performance plasma assays predicting burden central nervous system (CNS), this review compares twenty-one different manuscripts measurements 42 40 amino acid-long (Aβ42 Aβ40) predict CNS status. Methodologies quantitate Aβ42 peptides blood via immunoassay immunoprecipitation-mass spectrometry (IP-MS) were considered, their ability distinguish amyloidosis compared CSF as reference standards was evaluated. Recent studies indicate some IP-MS perform well precisely measuring detecting aggregates.

Language: Английский

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Astrocyte calcium dysfunction causes early network hyperactivity in Alzheimer’s disease

Cell Reports, Journal Year: 2022, Volume and Issue: 40(8), P. 111280 - 111280

Published: Aug. 1, 2022

Dysfunctions of network activity and functional connectivity (FC) represent early events in Alzheimer's disease (AD), but the underlying mechanisms remain unclear. Astrocytes regulate local neuronal healthy brain, their involvement hyperactivity AD is unknown. We show increased FC human cingulate cortex several years before amyloid deposition. find same disruption AppNL-F mice. Crucially, these disruptions are accompanied by decreased astrocyte calcium signaling. Recovery astrocytic normalizes FC, as well seizure susceptibility day/night behavioral disruptions. In conclusion, we that astrocytes mediate initial features drive clinically relevant phenotypes.

Language: Английский

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Aptamer-Functionalized Carbon Nanotube Field-Effect Transistor Biosensors for Alzheimer’s Disease Serum Biomarker Detection

ACS Sensors, Journal Year: 2022, Volume and Issue: 7(7), P. 2075 - 2083

Published: July 11, 2022

Blood-biomarker-based tests are highly important for the early clinical diagnosis of Alzheimer's disease (AD) and treatment care AD patients, but complex serum environment extremely low abundance blood protein biomarkers present challenges. Nanomaterials promising constructing sensitive transistor-based biosensors due to their small size. However, such difficult fabricate on a large scale suffer from lack combined optimization reproducibility sensitivity in physiological fluids. In this work, field-effect transistor (FET) based uniform semiconducting carbon nanotube (CNT) thin films mass produced achieve selective detection core β-amyloid (Aβ). The combination mass-produced CNT FET sensors oligonucleotide aptamers as efficient bioreceptors enables reliable reproducible sub-femtomolar full human Aβ42 Aβ40 peptides has outperformed other methods reported date. adsorption biological substrates sensor was significantly reduced by multiple blocking steps, resulting selectivity ratios up 730% (Aβ40) 800% (Aβ42). aptamer-functionalized biosensor exhibits dynamic range (>104), rapid response time (several minutes), variation (<10%) can be delivered low-cost technology screening AD. This platform will help bring laboratory-based expensive diagnostic tools point care.

Language: Английский

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Alzheimer blood biomarkers: practical guidelines for study design, sample collection, processing, biobanking, measurement and result reporting

Molecular Neurodegeneration, Journal Year: 2024, Volume and Issue: 19(1)

Published: May 15, 2024

Abstract Alzheimer’s disease (AD), the most common form of dementia, remains challenging to understand and treat despite decades research clinical investigation. This might be partly due a lack widely available cost-effective modalities for diagnosis prognosis. Recently, blood-based AD biomarker field has seen significant progress driven by technological advances, mainly improved analytical sensitivity precision assays measurement platforms. Several biomarkers have shown high potential accurately detecting pathophysiology. As result, there been considerable interest in applying these prognosis, as surrogate metrics investigate impact various covariates on pathophysiology accelerate therapeutic trials monitor treatment effects. However, standardization how blood samples collected, processed, stored analyzed reported can affect reproducibility measurements, potentially hindering toward their widespread use settings. To help address issues, we provide fundamental guidelines developed according recent findings sample handling measurements. These cover important considerations including study design, collection, processing, biobanking, measurement, result reporting. Furthermore, proposed include best practices appropriate procedures genetic ribonucleic acid analyses. While focus key AT(N) criteria (e.g., amyloid-beta [Aβ]40, Aβ42, Aβ42/40 ratio, total-tau, phosphorylated-tau, neurofilament light chain, brain-derived tau glial fibrillary acidic protein), anticipate that will generally applicable other types biomarkers. We also assist investigators planning executing research, enabling harmonization improve comparability across studies.

Language: Английский

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Blood-based high sensitivity measurements of beta-amyloid and phosphorylated tau as biomarkers of Alzheimer’s disease: a focused review on recent advances

Journal of Neurology Neurosurgery & Psychiatry, Journal Year: 2021, Volume and Issue: 92(11), P. 1231 - 1241

Published: Sept. 11, 2021

Discovery and development of clinically useful biomarkers for Alzheimer’s disease (AD) related dementias have been the focus recent research efforts. While cerebrospinal fluid positron emission tomography or MRI-based neuroimaging markers made in vivo detection AD pathology its consequences possible, high cost invasiveness limited their widespread use clinical setting. On other hand, advances potentially more accessible blood-based had impeded by lack sensitivity detecting changes hallmarks AD, including amyloid-β (Aβ) peptides phosphorylated tau (P-tau). More recently, however, emerging technologies with superior specificity measuring Aβ P-tau reported concordances severity. In this focused review, we describe several technologies, immunoprecipitation-mass spectrometry (IP-MS), single molecule array Meso Scale immunoassay platforms, appraise current literature arising from to identify plaques, tangles AD-associated pathology. there is potential utility adopting these also highlight further studies needed establish as validation existing large sample sets, new independent cohorts diverse backgrounds well population-based longitudinal studies. conclusion, availability sensitive reliable measurements species blood holds promise diagnosis, prognosis outcome assessments trials AD.

Language: Английский

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