Multi-analyte proteomic analysis identifies blood-based neuroinflammation, cerebrovascular and synaptic biomarkers in preclinical Alzheimer’s disease DOI Creative Commons
Xuemei Zeng,

Tara K Lafferty,

Anuradha Sehrawat

et al.

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

Published: Oct. 10, 2024

Blood-based biomarkers are gaining grounds for the detection of Alzheimer's disease (AD) and related disorders (ADRDs). However, two key obstacles remain: lack methods multi-analyte assessments need pathophysiological processes like neuroinflammation, vascular, synaptic dysfunction. A novel proteomic method pre-selected analytes, based on proximity extension technology, was recently introduced. Referred to as NULISAseq CNS panel, assay simultaneously measures ~ 120 analytes neurodegenerative diseases, including those linked both core (i.e., tau amyloid-beta (Aβ)) non-core AD processes. This study aimed evaluate technical clinical performance this targeted panel.

Language: Английский

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

et al.

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

Published: Jan. 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

Language: Английский

Citations

29
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

et al.

Science Translational Medicine, Journal Year: 2024, Volume and Issue: 16(753)

Published: June 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.

Language: Английский

Citations

18
Proteomic changes in Alzheimer disease associated with progressive Aβ plaque and tau tangle pathologies DOI Creative Commons
Alexa Pichet Binette, Chris Gaiteri, Malin Wennström

et al.

Nature Neuroscience, Journal Year: 2024, Volume and Issue: 27(10), P. 1880 - 1891

Published: Aug. 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.

Language: Английский

Citations

18
Longitudinal analysis of a dominantly inherited Alzheimer disease mutation carrier protected from dementia DOI
Jorge J. Llibre‐Guerra, María Victoria Fernández, Nelly Joseph‐Mathurin

et al.

Nature Medicine, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 10, 2025

Language: Английский

Citations

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

et al.

Computers in Biology and Medicine, Journal Year: 2024, Volume and Issue: 170, P. 108035 - 108035

Published: Feb. 3, 2024

Language: Английский

Citations

16
Multiplex cerebrospinal fluid proteomics identifies biomarkers for diagnosis and prediction of Alzheimer’s disease DOI

Yu Guo,

Shi-Dong Chen, Jia You

et al.

Nature Human Behaviour, Journal Year: 2024, Volume and Issue: 8(10), P. 2047 - 2066

Published: July 10, 2024

Language: Английский

Citations

15
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

et al.

Alzheimer s & Dementia, Journal Year: 2024, Volume and Issue: 20(6), P. 4043 - 4065

Published: May 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.

Language: Английский

Citations

13
Multi Omics Applications in Biological Systems DOI Creative Commons
Cristian D. Gutierrez Reyes, Gerardo Alejo‐Jacuinde, Benjamin Perez Sanchez

et al.

Current Issues in Molecular Biology, Journal Year: 2024, Volume and Issue: 46(6), P. 5777 - 5793

Published: June 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

Language: Английский

Citations

13
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

et al.

Cell Reports Medicine, Journal Year: 2024, Volume and Issue: 5(8), P. 101669 - 101669

Published: Aug. 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.

Language: Английский

Citations

13
Periodontitis and brain magnetic resonance imaging markers of Alzheimer's disease and cognitive aging DOI Creative Commons

Tom Rubinstein,

Adam M. Brickman, Bin Cheng

et al.

Alzheimer s & Dementia, Journal Year: 2024, Volume and Issue: 20(3), P. 2191 - 2208

Published: Jan. 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.

Language: Английский

Citations

12