Dataset Information

Shotgun-based Proteomics of Extracellular Vesicles in Alzheimer’s Disease Reveals Biomarkers Involved in Immunological and Coagulation Pathways

ABSTRACT: Alzheimer’s dementia (AD) is the most common form of dementia and without readily available clinical biomarkers. Blood-derived proteins are routinely used for diagnostics, however, comprehensive plasma profiling is challenging due to the large dynamic range in protein concentrations. Extracellular vesicles (EVs) can cross the blood-brain barrier and may provide a source for AD related biomarkers. We investigated plasma-derived EV proteins for biomarkers towards AD diagnostics from 10 AD patients, 10 Mild Cognitive Impairment (MCI) patients, and 9 healthy controls (Con) using liquid chromatography - tandem mass spectrometry (LC-MS/MS). EV enrichment was performed using a double centrifugation of 100,000 × g, 1h, 4°C with a wash of the pellet. Some AD patients presented with highly elevated FXIIIA1 (log2 FC: 4.6, p-value: 0.005) and FXIIIB (log2 FC: 4.9, p-value: 0.018). A group of proteins was identified discriminating Con and AD (AUC: 0.91, CI: 0.67-1.00) with ORM2 (AUC: 1.00, CI: 1.00-1.00), RBP4 (AUC: 0.99, CI: 0.95-1.00), and HYDIN (AUC: 0.89, CI: 0.72-1.00) found especially relevant for AD. This indicates that EVs provide an easily accessible matrix for possible biomarkers for AD. Some of the MCI patients, with similar protein profiles as the AD group progressed to AD within a 2-year timespan.

INSTRUMENT(S): Orbitrap Fusion

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Extracellular Vesicle, Blood

DISEASE(S): Alzheimer's Disease

SUBMITTER: Jonas Ellegaard Nielsen

LAB HEAD: Bent Honoré

PROVIDER: PXD024216 | Pride | 2022-02-16

REPOSITORIES: Pride

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Dataset's files

Source:

			Action	DRS
	150319_10_EV_9_PRO_S-Trap_micro_1ug_1_h_14_25_40_50cm.raw	Raw
	150319_11_EV_10_PRO_S-Trap_micro_1ug_1_h_14_25_40_50cm.raw	Raw
	150319_12_EV_11_PRO_S-Trap_micro_1ug_1_h_14_25_40_50cm.raw	Raw
	150319_13_EV_15_PRO_S-Trap_micro_1ug_1_h_14_25_40_50cm.raw	Raw
	150319_14_EV_16_PRO_S-Trap_micro_1ug_1_h_14_25_40_50cm.raw	Raw

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Publications

Shotgun-based proteomics of extracellular vesicles in Alzheimer's disease reveals biomarkers involved in immunological and coagulation pathways.

Nielsen Jonas Ellegaard JE Honoré Bent B Vestergård Karsten K Maltesen Raluca Georgiana RG Christiansen Gunna G Bøge Anna Uhd AU Kristensen Søren Risom SR Pedersen Shona S

Scientific reports 20210916 1

Alzheimer's disease (AD) is the most common form of dementia and without readily available clinical biomarkers. Blood-derived proteins are routinely used for diagnostics; however, comprehensive plasma profiling is challenging due to the dynamic range in protein concentrations. Extracellular vesicles (EVs) can cross the blood-brain barrier and may provide a source for AD biomarkers. We investigated plasma-derived EV proteins for AD biomarkers from 10 AD patients, 10 Mild Cognitive Impairment (MCI ...[more]

PMID: 34531462

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Project description:<h4>INTRODUCTION Alzheimer's disease is a prevalent disease with a heavy global burden and is suggested to be a metabolic disease in the brain in recent years. The metabolome is considered to be the most promising phenotype which reflects changes in genetic, transcript, and protein profiles as well as environmental effects. Aiming to obtain a comprehensive understanding and convenient diagnosis of MCI and AD from another perspective, researchers are working on AD metabolomics. Urine is more convenient which could reflect the change of disease at an earlier stage. Thus, we conducted a cross-sectional study to investigate novel diagnostic panels.</h4>METHODS We first enrolled participants from China-Japan Friendship Hospital from April 2022 to November 2022, collected urine samples and conducted an LC-MS/MS analysis. In parallel, clinical data were collected and clinical examinations were performed. After statistical and bioinformatics analyzes, significant risk factors and differential urinary metabolites were determined. We attempt to investigate diagnostic panels based on machine learning including LASSO and SVM.RESULTS 57 AD patients, 43 MCI patients and 62 CN subjects were enrolled. A total of 2,140 metabolites were identified among which 125 significantly differed between the AD and CN groups, including 46 upregulated ones and 79 downregulated ones. In parallel, there were 93 significant differential metabolites between the MCI and CN groups, including 23 upregulated ones and 70 downregulated ones. AD diagnostic panel (30 metabolites+ age + APOE) achieved an AUC of 0.9575 in the test set while MCI diagnostic panel (45 metabolites+ age + APOE) achieved an AUC of 0.7333 in the test set. Atropine, S-Methyl-L-cysteine-S-oxide, D-Mannose 6-phosphate (M6P), Spiculisporic Acid, N-Acetyl-L-methionine, 13,14-dihydro-15-keto-tetranor Prostaglandin D2, Pyridoxal 5'-Phosphate (PLP) and 17(S)-HpDHA were considered valuable for both AD and MCI diagnosis and defined as hub metabolites. Besides, diagnostic metabolites were weakly correlated with cognitive functions.DISCUSSION In conclusion, the procedure is convenient, non-invasive, and useful for diagnosis, which could assist physicians in differentiating AD and MCI from CN. Atropine, M6P and PLP were evidence-based hub metabolites in AD.