Emerging nanotechnology for Alzheimer's disease: From detection to treatment DOI
Nan Song, Si Sun, Ke Chen

et al.

Journal of Controlled Release, Journal Year: 2023, Volume and Issue: 360, P. 392 - 417

Published: July 10, 2023

Language: Английский

Comparison of plasma neurofilament light and total tau as neurodegeneration markers: associations with cognitive and neuroimaging outcomes DOI Creative Commons
Jordan D. Marks, Jeremy A. Syrjanen, Jonathan Graff‐Radford

et al.

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

Published: Dec. 1, 2021

Total tau protein (T-Tau) and neurofilament light chain (NfL) have emerged as candidate plasma biomarkers of neurodegeneration, but studies not compared how these cross-sectionally or longitudinally associate with cognitive neuroimaging measures. We therefore T-Tau NfL cross-sectional longitudinal markers (1) global domain-specific decline (2) cortical thickness, hippocampal volume, white matter integrity, hyperintensity volume.We included 995 participants without dementia who were enrolled in the Mayo Clinic Study Aging cohort. All had concurrent T-tau, status, data. Follow-up was repeated approximately every 15 months for a median 6.2 years. Plasma T-tau measured on Simoa-HD1 Platform. Linear mixed effects models adjusted age, sex, education examined associations between baseline z-scored outcomes. Analyses replicated Alzheimer's Disease Neuroimaging Initiative (ADNI) among 387 followed 3.0 years.At baseline, more strongly associated all The combination having both elevated at to levels either alone, cross-section worse cognition memory, measures including temporal cortex thickness increased number infarcts. In analyses, did add prognostic value NfL. Results using ADNI data similar.Our results indicate better utility marker changes. added specific contexts.Not applicable.

Language: Английский

Citations

61

Uncovering the Depths of the Human Proteome: Antibody-based Technologies for Ultrasensitive Multiplexed Protein Detection and Quantification DOI Creative Commons

Annie Ren,

Eleftherios P. Diamandis, Vathany Kulasingam

et al.

Molecular & Cellular Proteomics, Journal Year: 2021, Volume and Issue: 20, P. 100155 - 100155

Published: Jan. 1, 2021

Probing the human proteome in tissues and biofluids such as plasma is attractive for biomarker drug target discovery. Recent breakthroughs multiplex, antibody-based, proteomics technologies now enable simultaneous quantification of thousands proteins at low sub fg/ml concentrations with remarkable dynamic ranges up to 10-log. We herein provide a comprehensive guide methodologies, performance, technical comparisons, advantages, disadvantages established emerging multiplexed ultrasensitive measurement proteins. Gaining holistic knowledge on these innovations crucial choosing right tool applications hand critically complement traditional methods. This can bring researchers closer than ever before elucidating intricate inner workings cross talk that spans multitude disease mechanisms.

Language: Английский

Citations

60

Association of plasma biomarkers, p‐tau181, glial fibrillary acidic protein, and neurofilament light, with intermediate and long‐term clinical Alzheimer's disease risk: Results from a prospective cohort followed over 17 years DOI Creative Commons
Hannah Stocker, Léon Beyer,

Laura Perna

et al.

Alzheimer s & Dementia, Journal Year: 2022, Volume and Issue: 19(1), P. 25 - 35

Published: March 2, 2022

Abstract Introduction Blood biomarkers for Alzheimer's disease (AD) are the future of AD risk assessment. The aim this study was to determine association between plasma‐measured phosphorylated tau (p‐tau181), glial fibrillary acidic protein (GFAP), and neurofilament light (NfL) levels clinical incidence with consideration impact cardiovascular health. Methods Within a community‐based cohort, biomarker were measured at baseline using single molecule array technology in 768 participants (aged 50–75) followed over 17 years. Associations among AD, vascular dementia, mixed dementia assessed. Results GFAP associated even more than decade before diagnosis (9–17 years), while p‐tau181 NfL intermediate (within 9 years). Significant interaction detected health p‐tau181/NfL. Discussion may be an early increasing effect modifying role should considered stratification.

Language: Английский

Citations

58

The Longitudinal Early‐onset Alzheimer's Disease Study (LEADS): Framework and methodology DOI Creative Commons
Liana G. Apostolova, Paul Aisen, Ani Eloyan

et al.

Alzheimer s & Dementia, Journal Year: 2021, Volume and Issue: 17(12), P. 2043 - 2055

Published: May 21, 2021

Abstract Patients with early‐onset Alzheimer's disease (EOAD) are commonly excluded from large‐scale observational and therapeutic studies due to their young age, atypical presentation, or absence of pathogenic mutations. The goals the Longitudinal EOAD Study (LEADS) (1) define clinical, imaging, fluid biomarker characteristics EOAD; (2) develop sensitive cognitive measures for future clinical research use; (3) establish a trial‐ready network. LEADS will follow 400 amyloid beta (Aβ)‐positive EOAD, 200 Aβ‐negative EOnonAD that meet National Institute on Aging–Alzheimer's Association (NIA‐AA) criteria mild impairment (MCI) AD dementia, 100 age‐matched controls. Participants undergo assessments, magnetic resonance imaging (MRI), [ 18 F]Florbetaben F]Flortaucipir positron emission tomography (PET), lumbar puncture, blood draw DNA, RNA, plasma, serum peripheral mononuclear cells, post‐mortem assessment. To more effective treatments, scientists need understand genetic, biological, processes involved in EOAD. public resource enable planning implementation trials.

Language: Английский

Citations

57

A microRNA signature that correlates with cognition and is a target against cognitive decline DOI
Rezaul Islam, Lalit Kaurani,

Tea Berulava

et al.

EMBO Molecular Medicine, Journal Year: 2021, Volume and Issue: 13(11)

Published: Oct. 11, 2021

Language: Английский

Citations

56

Ultrahigh Sensitive Detection of Tau Protein as Alzheimer's Biomarker via Microfluidics and Nanofunctionalized Optical Fiber Sensors DOI Creative Commons
Francesco Chiavaioli, Desiree Santano, Ignacio Del Villar

et al.

Advanced Photonics Research, Journal Year: 2022, Volume and Issue: 3(11)

Published: July 18, 2022

Alzheimer's disease (AD) is one of the most common neurodegenerative illnesses displaying highest death rate in elderly. However, existing AD diagnostic system remains elusive due to lack a technology that may ensure enough sensitivity and reproducibility, detection accuracy, specificity. Herein, straightforward approach reported realize lab‐on‐fiber (LoF) for biomarker based on D‐shaped single‐mode fiber combined with nanometer‐scale metal‐oxide film. The proposed sensing system, which permits generation lossy‐mode resonance (LMR), remarkably increases evanescent field light guided through fiber, hence fiber‐surrounding medium interaction. Moreover, such optical sensors are highly repeatable results can safely be embedded into compact stable microfluidic system. specific Tau protein (as classical biomarkers correlated progression) complex biofluid limit 10 −12 m over wide concentration range (10 −3 –10 μg mL −1 ) successfully demonstrated. LoF biosensor an appealing solution rapid, sub‐microliter dose sensitive analytes at low concentrations, hereby having potential toward early screening personalized medicine AD.

Language: Английский

Citations

56

Neurofilament light chain concentration in an aging population DOI Creative Commons
Aurélie Ladang, Stéphanie Kovacs, Laetitia Lengelé

et al.

Aging Clinical and Experimental Research, Journal Year: 2022, Volume and Issue: 34(2), P. 331 - 339

Published: Jan. 11, 2022

Neurofilament light chain (NF-L) concentration is recognized to be modified in neurological diseases and traumatic brain injuries, but studies the normal aging population are lacking. It is, therefore, urgent identify influencing factors of NF-L population.We assessed sera a large cohort 409 community-dwelling adults aged over 65 years. We studied association between various physiological also with self-reported comorbidities or life-style habits.We showed that serum was tightly associated cystatin C (r = 0.501, p < 0.0001) consequently, estimated glomerular filtration rate (eGFR) - 0.492; 0.0001). Additionally, dependent on age body mass index (BMI) not sex. Among comorbidities, subjects who reported disorders, cardiovascular history fracture had higher univariate analysis, whereas it only case for disorders multivariate analysis. increased when Mini-Mental State Examination (MMSE) decreased (≤ 25 points) geriatric depression score (GDS) (> 5 both Finally, we providing reference ranges by categories without altered renal function.NF-L driven increasing number depression. Yet, blood kidney function interpretation patients suffering from failure should taken caution.

Language: Английский

Citations

53

Amyloid‐beta misfolding and GFAP predict risk of clinical Alzheimer's disease diagnosis within 17 years DOI Creative Commons
Léon Beyer, Hannah Stocker, Dan Rujescu

et al.

Alzheimer s & Dementia, Journal Year: 2022, Volume and Issue: 19(3), P. 1020 - 1028

Published: July 19, 2022

Abstract Introduction Blood‐based biomarkers for Alzheimer's disease (AD) are urgently needed. Here, four plasma were measured at baseline in a community‐based cohort followed over 17 years, and the association with clinical AD risk was determined. Methods Amyloid beta (Aβ) misfolding status as structure‐based biomarker well phosphorylated tau 181 (P‐tau181), glial fibrillary acidic protein (GFAP), neurofilament light (NfL) concentration levels determined heparin from 68 participants who diagnosed 240 controls without dementia diagnosis throughout follow‐up. Results Aβ exhibited high prediction accuracy of within years. Among markers, GFAP showed best performance, by NfL P‐tau181. The combination increased accuracy. Discussion strong ability to predict may be important early markers. illustrated its potential prescreening tool stratification older adults.

Language: Английский

Citations

50

Plasma biomarkers for diagnosis of Alzheimer's disease and prediction of cognitive decline in individuals with mild cognitive impairment DOI Creative Commons
Pia Kivisäkk, Becky C. Carlyle,

Thadryan Sweeney

et al.

Frontiers in Neurology, Journal Year: 2023, Volume and Issue: 14

Published: March 2, 2023

Background The last few years have seen major advances in blood biomarkers for Alzheimer's Disease (AD) with the development of ultrasensitive immunoassays, promising to transform how we diagnose, prognose, and track progression neurodegenerative dementias. Methods We evaluated a panel four novel electrochemiluminescence (ECL) immunoassays against presumed CNS derived proteins interest AD plasma [phosphorylated-Tau181 (pTau181), total Tau (tTau), neurofilament light (NfL), glial fibrillary acidic protein (GFAP)]. Two sets banked samples from Massachusetts Research Center's longitudinal cohort study were examined: A prognostic sample ( n = 85) consisting individuals mild cognitive impairment (MCI) 4 follow-up cross-sectional 238) AD, other diseases (OND), normal cognition (CN). Results Participants MCI who progressed dementia due probable during had higher baseline concentrations pTau181, NfL, GFAP compared non-progressors. best discrimination was observed pTau181 (AUC 0.83, 1.7-fold increase) 1.6-fold increase). autopsy- and/or biomarker verified levels tTau CN OND, while NfL elevated further increased OND. diagnostic (AD vs CN: AUC 0.90, 2-fold increase; vs. OND: 0.84, 1.5-fold but tTau, also showed good between 0.81–0.85; 1.5–2.2 fold Conclusions These new ECL assays demonstrated utility detection AD. Moreover, absolute reflect decline over next years, providing information that may both clinical practice trial populations.

Language: Английский

Citations

38

Digital detection of proteins DOI Open Access
David C. Duffy

Lab on a Chip, Journal Year: 2023, Volume and Issue: 23(5), P. 818 - 847

Published: Jan. 1, 2023

We review innovations in digital protein detection that has greatly improved the sensitivity of immunoassays and their impact on biomedicine.

Language: Английский

Citations

33