Benchmarking of a multi‐biomarker low‐volume panel for Alzheimer's disease and related dementia research DOI Creative Commons
Laura Ibáñez, Menghan Liu, Aleksandra Beric

и другие.

Alzheimer s & Dementia, Год журнала: 2024, Номер unknown

Опубликована: Ноя. 22, 2024

Abstract INTRODUCTION In the research setting, obtaining accurate established biomarker measurements and maximizing use of precious samples is key. Accurate technologies are available for Alzheimer's disease (AD), but no platform can measure all emerging biomarkers in one run. The NUcleic acid Linked Immuno‐Sandwich Assay (NULISA) a technology that requires 15 µL sample to more than 100 analytes. METHODS We compared AD‐relevant included NULISA against validated assays cerebrospinal fluid (CSF) plasma. RESULTS CSF measures amyloid beta 42/40, phosphorylated tau (p‐tau)217 highly correlated when measured by immunoassay, mass spectrometry, or NULISA. plasma, p‐tau217 performance similar reported with other predicting amyloidosis. Other show wide range correlation values depending on platform. DISCUSSION multiplexed produces reliable results useful settings, advantage measuring additional using minimal volume. Highlights tested novel dementia setting. Cerebrospinal

Язык: Английский

Fluid biomarkers for amyotrophic lateral sclerosis: a review DOI Creative Commons
Katherine E. Irwin, Udit Sheth, Philip C. Wong

и другие.

Molecular Neurodegeneration, Год журнала: 2024, Номер 19(1)

Опубликована: Янв. 24, 2024

Abstract Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease characterized by the loss of upper and lower motor neurons. Presently, three FDA-approved drugs are available to help slow functional decline for patients with ALS, but no cure yet exists. With an average life expectancy only two five years after diagnosis, there clear need biomarkers improve care ALS expedite treatment development. Here, we provide review efforts made towards identifying diagnostic, prognostic, susceptibility/risk, response fluid intent facilitate more rapid accurate better predict prognosis, clinical trial design, inform interpretation results. Over course 20 + years, several promising biomarker candidates have emerged. These will be discussed, as exciting new strategies being explored discovery

Язык: Английский

Процитировано

28
Proteomic analysis of Alzheimer’s disease cerebrospinal fluid reveals alterations associated with APOE ε4 and atomoxetine treatment DOI Open Access
Eric B. Dammer, Anantharaman Shantaraman, Lingyan Ping

и другие.

Science Translational Medicine, Год журнала: 2024, Номер 16(753)

Опубликована: Июнь 26, 2024

Alzheimer’s disease (AD) is currently defined by the aggregation of amyloid-β (Aβ) and tau proteins in brain. Although biofluid biomarkers are available to measure Aβ pathology, few markers complex pathophysiology that associated with these two cardinal neuropathologies. Here, we characterized proteomic landscape cerebrospinal fluid (CSF) changes pathology 300 individuals using different technologies—tandem mass tag spectrometry SomaScan. Integration both data types allowed for generation a robust protein coexpression network consisting 34 modules derived from 5242 measurements, including disease-relevant autophagy, ubiquitination, endocytosis, glycolysis. Three strongly apolipoprotein E ε4 ( APOE ε4) AD risk genotype mapped oxidant detoxification, mitogen-associated kinase signaling, neddylation, mitochondrial biology overlapped previously described lipoprotein module serum. Alterations all three blood were dementia more than 20 years before diagnosis. Analysis CSF samples an phase 2 clinical trial atomoxetine (ATX) demonstrated abnormal elevations glycolysis module—the most correlated cognitive function—were reduced ATX treatment. Clustering based on their profiles revealed heterogeneity pathological not fully reflected tau.

Язык: Английский

Процитировано

16
Proteomic changes in Alzheimer disease associated with progressive Aβ plaque and tau tangle pathologies DOI Creative Commons
Alexa Pichet Binette, Chris Gaiteri, Malin Wennström

и другие.

Nature Neuroscience, Год журнала: 2024, Номер 27(10), С. 1880 - 1891

Опубликована: Авг. 26, 2024

Abstract Proteomics can shed light on the dynamic and multifaceted alterations in neurodegenerative disorders like Alzheimer’s disease (AD). Combining radioligands measuring β-amyloid (Aβ) plaques tau tangles with cerebrospinal fluid proteomics, we uncover molecular events mirroring different stages of AD pathology living humans. We found 127 differentially abundant proteins (DAPs) across spectrum. The strongest Aβ-related were mainly expressed glial cells included SMOC1 ITGAM. A dozen linked to ATP metabolism preferentially neurons independently associated tangle load accumulation. Only 20% DAPs also altered other diseases, underscoring AD’s distinct proteome. Two co-expression modules related, respectively, protein microglial immune response encompassed most DAPs, opposing, staggered trajectories along continuum. unveil signatures Aβ proteinopathy vivo, offering insights into complex neural responses potential biomarkers therapeutics targeting stages.

Язык: Английский

Процитировано

16
Longitudinal analysis of a dominantly inherited Alzheimer disease mutation carrier protected from dementia DOI
Jorge J. Llibre‐Guerra, María Victoria Fernández, Nelly Joseph‐Mathurin

и другие.

Nature Medicine, Год журнала: 2025, Номер unknown

Опубликована: Фев. 10, 2025

Язык: Английский

Процитировано

3
A hybrid multimodal machine learning model for Detecting Alzheimer's disease DOI
Jinhua Sheng, Qian Zhang, Qiao Zhang

и другие.

Computers in Biology and Medicine, Год журнала: 2024, Номер 170, С. 108035 - 108035

Опубликована: Фев. 3, 2024

Язык: Английский

Процитировано

14
Multiplex cerebrospinal fluid proteomics identifies biomarkers for diagnosis and prediction of Alzheimer’s disease DOI

Yu Guo,

Shi-Dong Chen, Jia You

и другие.

Nature Human Behaviour, Год журнала: 2024, Номер 8(10), С. 2047 - 2066

Опубликована: Июль 10, 2024

Язык: Английский

Процитировано

13
Proteomic changes in the human cerebrovasculature in Alzheimer's disease and related tauopathies linked to peripheral biomarkers in plasma and cerebrospinal fluid DOI Creative Commons

Aleksandra Wojtas,

Eric B. Dammer, Qi Guo

и другие.

Alzheimer s & Dementia, Год журнала: 2024, Номер 20(6), С. 4043 - 4065

Опубликована: Май 7, 2024

Cerebrovascular dysfunction is a pathological hallmark of Alzheimer's disease (AD). Nevertheless, detecting cerebrovascular changes within bulk tissues has limited our ability to characterize proteomic alterations from less abundant cell types.

Язык: Английский

Процитировано

12
Multi Omics Applications in Biological Systems DOI Creative Commons
Cristian D. Gutierrez Reyes, Gerardo Alejo‐Jacuinde, Benjamin Perez Sanchez

и другие.

Current Issues in Molecular Biology, Год журнала: 2024, Номер 46(6), С. 5777 - 5793

Опубликована: Июнь 11, 2024

Traditional methodologies often fall short in addressing the complexity of biological systems. In this regard, system biology omics have brought invaluable tools for conducting comprehensive analysis. Current sequencing capabilities revolutionized genetics and genomics studies, as well characterization transcriptional profiling dynamics several species sample types. Biological systems experience complex biochemical processes involving thousands molecules. These occur at different levels that can be studied using mass spectrometry-based (MS-based) analysis, enabling high-throughput proteomics, glycoproteomics, glycomics, metabolomics, lipidomics Here, we present most up-to-date techniques utilized completion Additionally, include some interesting examples applicability multi to a variety

Язык: Английский

Процитировано

12
Integrative proteomics identifies a conserved Aβ amyloid responsome, novel plaque proteins, and pathology modifiers in Alzheimer’s disease DOI Creative Commons
Yona Levites, Eric B. Dammer,

Yong Ran

и другие.

Cell Reports Medicine, Год журнала: 2024, Номер 5(8), С. 101669 - 101669

Опубликована: Авг. 1, 2024

Alzheimer's disease (AD) is a complex neurodegenerative disorder that develops over decades. AD brain proteomics reveals vast alterations in protein levels and numerous altered biologic pathways. Here, we compare proteome network changes with the proteomes of amyloid β (Aβ)-depositing mice to identify conserved divergent networks identifying an Aβ responsome. Proteins most (M42) accumulate plaques, cerebrovascular (CAA), and/or dystrophic neuronal processes, overexpression two M42 proteins, midkine (Mdk) pleiotrophin (PTN), increases accumulation plaques CAA. proteins bind fibrils vitro, MDK PTN co-accumulate cardiac transthyretin amyloid. appear intimately linked deposition can regulate deposition, suggesting they are pathology modifiers thus putative therapeutic targets. We posit amyloid-scaffolded M42+ central mechanism mediating downstream pathophysiology AD.

Язык: Английский

Процитировано

11
Periodontitis and brain magnetic resonance imaging markers of Alzheimer's disease and cognitive aging DOI Creative Commons

Tom Rubinstein,

Adam M. Brickman, Bin Cheng

и другие.

Alzheimer s & Dementia, Год журнала: 2024, Номер 20(3), С. 2191 - 2208

Опубликована: Янв. 26, 2024

Abstract INTRODUCTION We examined the association of clinical, microbiological, and host response features periodontitis with MRI markers atrophy/cerebrovascular disease in Washington Heights Inwood Columbia Aging Project (WHICAP) Ancillary Study Oral Health. METHODS analyzed 468 participants clinical periodontal data, microbial plaque serum samples, brain MRIs. tested features, after adjusting for multiple risk factors Alzheimer's disease/Alzheimer's disease‐related dementia (AD/ADRD). RESULTS In fully adjusted models, having more teeth was associated lower odds infarcts, white matter hyperintensity (WMH) volume, higher entorhinal cortex cortical thickness. Higher extent volume Differential associations emerged between colonization by specific bacteria/serum antibacterial IgG responses outcomes. DISCUSSION an elderly cohort, serological were findings related to ADRD risk. Further investigation causal is warranted.

Язык: Английский

Процитировано

9