Mass-spectrometry-based proteomics: from single cells to clinical applications

Nature, Journal Year: 2025, Volume and Issue: 638(8052), P. 901 - 911

Published: Feb. 26, 2025

Language: Английский

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Integrative proteomics identifies a conserved Aβ amyloid responsome, novel plaque proteins, and pathology modifiers in Alzheimer’s disease

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

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Integrating amyloid and tau imaging with proteomics and genomics in Alzheimer’s disease

Cell Reports Medicine, Journal Year: 2024, Volume and Issue: 5(9), P. 101735 - 101735

Published: Sept. 1, 2024

Language: Английский

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The effect of thermal stress on the X-organ/sinus gland proteome of the estuarine blue crab Callinectes sapidus during the intermolt and premolt stages

Journal of Proteomics, Journal Year: 2025, Volume and Issue: 313, P. 105382 - 105382

Published: Jan. 10, 2025

Language: Английский

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High-Throughput Human Cerebrospinal Fluid Proteome Analysis with Direct Data-Independent Acquisition (dDIA)

Methods in molecular biology, Journal Year: 2025, Volume and Issue: unknown, P. 129 - 139

Published: Jan. 1, 2025

Language: Английский

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Unraveling Potential Tauopathy Biomarkers in Cerebrospinal Fluid: Insights from Olfactory Tract Data

Methods in molecular biology, Journal Year: 2025, Volume and Issue: unknown, P. 261 - 273

Published: Jan. 1, 2025

Language: Английский

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CAA proteomics meta-analysis reveals novel targets, key players, and the effects of sex, APOE, and brain region in humans

Acta Neuropathologica, Journal Year: 2025, Volume and Issue: 149(1)

Published: April 29, 2025

Language: Английский

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Aβ Amyloid Scaffolds the Accumulation of Matrisome and Additional Proteins in Alzheimer’s Disease

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2023, Volume and Issue: unknown

Published: Dec. 1, 2023

We report a highly significant correlation in brain proteome changes between Alzheimers disease (AD) and CRND8 APP695NL/F transgenic mice. However, integrating protein observed the mice with co-expression networks derived from human AD, reveals both conserved divergent module changes. For most (M42, matrisome) we find many proteins accumulate plaques, cerebrovascular amyloid (CAA), dystrophic processes, or combination thereof. Overexpression of two M42 proteins, midkine (Mdk) pleiotrophin (PTN), brains leads to increased accumulation A β ; plaques CAA; further, recombinant MDK PTN enhance aggregation into amyloid. Multiple annotated as heparan sulfate binding bind fibrillar 42 non-human fibril vitro. Supporting this data, co-accumulate transthyretin (TTR) heart islet polypeptide (IAPP) pancreas. Our findings establish several critical insights. Proteomic modules AD define an responsome that is well mouse model human. Further, distinct structures may serve scaffolds, facilitating co-accumulation signaling functions. hypothesize contribute downstream pathological sequalae. Overall, contextualized understanding proteomic their interplay deposition provides valuable insights complexity pathogenesis potential biomarkers therapeutic targets.

Language: Английский

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Potential diagnostic value of CSF metabolism-related proteins across the Alzheimer’s disease continuum

Alzheimer s Research & Therapy, Journal Year: 2023, Volume and Issue: 15(1)

Published: July 15, 2023

Abstract Background Alzheimer’s disease (AD) cerebrospinal fluid (CSF) core biomarkers (Aβ42/40 ratio, p-tau, and t-tau) provide high diagnostic accuracy, even at the earliest stage of disease. However, these markers do not fully reflect complex AD pathophysiology. Recent large scale CSF proteomic studies revealed several new candidate related to metabolic pathways. In this study we measured levels four metabolism-related proteins directly linked amyloid- tau-pathways (i.e., pyruvate kinase, PKM; aldolase, ALDO; ubiquitin C-terminal hydrolase L1, UCHL1, fatty acid-binding protein 3, FABP3) across continuum. We aimed validating potential value as for their possible involvement in pathogenesis, with specific interest on preclinical phase Methods PKM ALDO activities were enzyme assays while UCHL1 FABP3 immunoassays a cohort patients composed follows: (pre-AD, n = 19, cognitively unimpaired), mild cognitive impairment due (MCI-AD, 50), dementia (ADdem, 45), frontotemporal (FTD, 37). Individuals MCI (MCI, 30) subjective decline (SCD, 52) negative AD-profile, enrolled control groups. Results levels, activity significantly increased patients, already pre-clinical stage. was also FTD compared groups, being similar between patients. No difference found among showed good performance discriminating early (pre-AD MCI-AD) from controls (AUC ~ 0.83), assessed by ROC analysis. Similar results obtained FABP3. Conversely, provided best when comparing vs. 0.80). Combination PKM, FABP3, improved accuracy detection within continuum single biomarkers. Conclusions Our confirmed role neurodegenerative AD. Furthermore, our validated increase Increased observed possibly underlining alterations energy metabolism FTD.

Language: Английский

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Are We Ready to Reclassify Crohn’s Disease Using Molecular Classification?

Journal of Clinical Medicine, Journal Year: 2023, Volume and Issue: 12(18), P. 5786 - 5786

Published: Sept. 5, 2023

Crohn’s disease (CD) is a type of inflammatory bowel disease. The number IBD cases worldwide was estimated to be 4.9 million in 2019. CD exhibits heterogeneity clinical presentation, anatomical involvement, behaviour, course and response treatment. classical description involves transmural inflammation with skip lesions anywhere along the entire gastrointestinal tract. complexity not currently reflected conventional classification system. Though knowledge pathophysiology remains far from understood, established complex interplay omics—genomics, transcriptomics, proteomics, epigenomics, metagenomics, metabolomics, lipidomics immunophenomics—provides numerous targets for potential molecular markers Advancing technology has enabled identification small molecules within these omics, which can extrapolated differentiate types multi-omic future promising, advancements understanding its pathogenesis implementation personalised medicine.

Language: Английский

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