Emergence of Extracellular Vesicles as “Liquid Biopsy” for Neurological Disorders: Boom or Bust

Pharmacological Reviews, Journal Year: 2023, Volume and Issue: 76(2), P. 199 - 227

Published: Dec. 19, 2023

Abstract

Extracellular vesicles (EVs) have emerged as an attractive liquid biopsy approach in the diagnosis and prognosis of multiple diseases disorders. The feasibility enriching specific subpopulations EVs from biofluids based on their unique surface markers has opened novel opportunities to gain molecular insight various tissues organs, including brain. Over past decade, bodily fluids been extensively studied for biomarkers associated with neurological disorders, such Alzheimer9s disease, Parkinson9s schizophrenia, bipolar disorder, major depressive substance use human immunodeficiency virus–associated neurocognitive cancer/treatment-induced neurodegeneration. These studies focused isolation cargo characterization either total or brain cells, neuron-, astrocyte-, microglia-, oligodendrocyte-, pericyte-, endothelial-derived achieve early predict treatment intervention outcomes. findings these demonstrated that could serve a repetitive less invasive source valuable information supplementing existing costly neuroimaging techniques relatively measures, like lumbar puncture. However, initial excitement surrounding blood-based brain-related tempered by challenges, lack central nervous system specificity EV markers, lengthy protocols, absence standardized procedures biological sample collection, isolation, characterization. Nevertheless, rapid advancements field, supported improved methods sensitive assays characterization, cell–derived continue offer unparallel significant translational implications

Significance Statement

present Characterizing holds potential yield information, thereby significantly impacting development This paper reviewed methodology employed isolate extracellular derived cells biofluids, utility enhancing understanding neurodegeneration, challenges this research field.

Language: Английский

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Unraveling the role of miRNAs in the diagnosis, progression, and therapeutic intervention of Alzheimer’s disease

Pathology - Research and Practice, Journal Year: 2023, Volume and Issue: 253, P. 155007 - 155007

Published: Dec. 4, 2023

Language: Английский

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Alzheimer’s disease biomarkers and their current use in clinical research and practice

Molecular Psychiatry, Journal Year: 2024, Volume and Issue: unknown

Published: Sept. 4, 2024

Language: Английский

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Novel method for collecting hippocampal interstitial fluid extracellular vesicles (EV^ISF) reveals sex‐dependent changes in microglial EV proteome in response to Aβ pathology

Journal of Extracellular Vesicles, Journal Year: 2024, Volume and Issue: 13(1)

Published: Jan. 1, 2024

Abstract Brain‐derived extracellular vesicles (EVs) play an active role in Alzheimer's disease (AD), relaying important physiological information about their host tissues. The internal cargo of EVs is protected from degradation, making attractive AD biomarkers. However, it unclear how circulating relate to isolated disease‐vulnerable brain regions. We developed a novel method for collecting the hippocampal interstitial fluid (ISF) live mice. (EV ISF ) were via ultracentrifugation and characterized by nanoparticle tracking analysis, immunogold labelling, flow cytometry. Mass spectrometry proteomic analyses performed on EV cargo. 40–150 nm size expressed CD63, CD9, CD81. Using model cerebral amyloidosis (e.g., APPswe , PSEN1dE9 mice), we found protein concentration increased but diversity decreased with Aβ deposition. Genotype, age, deposition modulated proteostasis‐ immunometabolic‐related pathways. Changes microglial proteome sexually dimorphic associated differential response plaque microglia. that female APP/PS1 mice have more amyloid plaques, less microglia, robust‐ diverse‐ proteome. Thus, vivo microdialysis technique offers unique opportunity explore AD.

Language: Английский

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Characterisation of LPS+ bacterial extracellular vesicles along the gut‐hepatic portal vein‐liver axis

Journal of Extracellular Vesicles, Journal Year: 2024, Volume and Issue: 13(7)

Published: July 1, 2024

Abstract Gut microbiome dysbiosis is a major contributing factor to several pathological conditions. However, the mechanistic understanding of communication between gut microbiota and extra‐intestinal organs remains largely elusive. Extracellular vesicles (EVs), secreted by almost every form life, including bacteria, could play critical role in this inter‐kingdom crosstalk are focus present study. Here, we novel approach for isolating lipopolysaccharide (LPS)+ bacterial extracellular (bEV LPS ) from complex biological samples, faeces, plasma liver lean diet‐induced obese (DIO) mice. bEV were extensively characterised using nanoparticle tracking analyses, immunogold labelling coupled with transmission electron microscopy, flow cytometry, super‐resolution microscopy 16S sequencing. In tissues, protein expressions TLR4 few macrophage‐specific biomarkers assessed immunohistochemistry, gene inflammation‐related cytokines their receptors ( n = 89 genes) measured PCR array. Faecal samples DIO mice revealed remarkably lower concentration total EVs but significantly higher percentage LPS+ EVs. Interestingly, faecal showed abundance Proteobacteria Importantly, mice, number consistently entered hepatic portal vein subsequently reached liver, associated increased expression TLR4, macrophage markers (F4/80, CD86 CD206), Il1rn , Ccr1 Cxcl10 Il2rg Ccr2 ). Furthermore, portion escaped peripheral circulation. conclusion, be key mediator orchestrating various well‐established effects induced bacteria on distant organs.

Language: Английский

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Posterior cingulate cortex microRNA dysregulation differentiates cognitive resilience, mild cognitive impairment, and Alzheimer's disease

Alzheimer s & Dementia, Journal Year: 2025, Volume and Issue: 21(2)

Published: Feb. 1, 2025

Abstract INTRODUCTION MicroRNA (miRNA) activity is increasingly appreciated as a key regulator of pathophysiologic pathways in Alzheimer's disease (AD). However, the role miRNAs during progression AD, including resilience and prodromal syndromes such mild cognitive impairment (MCI), remains underexplored. METHODS We performed miRNA‐sequencing on samples posterior cingulate cortex (PCC) obtained post mortem from Rush Religious Orders Study participants diagnosed ante with no (NCI), MCI, or AD. NCI subjects were subdivided low pathology (Braak stage I/II) high III/IV), suggestive resilience. Bioinformatics approaches included differential expression, messenger RNA (mRNA) target prediction, interactome modeling, functional enrichment, AD risk modeling. RESULTS identified specific miRNA groups, mRNA targets, signaling distinguishing resilience, neuropsychological test performance, neuropathological burden, risk. DISCUSSION These findings highlight potential harnessing to manipulate disease‐modifying implications for precision medicine. Highlights (MiRNA) dysregulation well‐established feature Novel also distinguish putative MiRNAs correlate performance burden. Select are associated age significant covariate. MiRNA include insulin, prolactin, kinases, neurite plasticity.

Language: Английский

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Therapeutic efficacy and promise of stem cell-derived extracellular vesicles in Alzheimer’s disease and other aging-related disorders

Ageing Research Reviews, Journal Year: 2023, Volume and Issue: 92, P. 102088 - 102088

Published: Oct. 11, 2023

Language: Английский

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Blood-based CNS regionally and neuronally enriched extracellular vesicles carrying pTau217 for Alzheimer’s disease diagnosis and differential diagnosis

Acta Neuropathologica Communications, Journal Year: 2024, Volume and Issue: 12(1)

Published: March 5, 2024

Abstract Accurate differential diagnosis among various dementias is crucial for effective treatment of Alzheimer’s disease (AD). The study began with searching novel blood-based neuronal extracellular vesicles (EVs) that are more enriched in the brain regions vulnerable to AD development and progression. With extensive proteomic profiling, GABRD GPR162 were identified as regionally plasma EVs markers. performance GPR162, along molecule pTau217, was tested using self-developed optimized nanoflow cytometry-based technology, which not only detected positive ratio but also concurrently presented corresponding particle size EVs, discovery (n = 310) validation 213) cohorts. Plasma + - or -carrying pTau217-EVs significantly reduced compared healthy control (HC). Additionally, distribution different between non-AD dementia (NAD). An integrative model, combining age, number pTau217-EVs, accurately sensitively discriminated from HC [discovery cohort, area under curve (AUC) 0.96; AUC 0.93] effectively differentiated NAD (discovery 0.91; 0.90). This showed carrying pTau217 may serve a robust diagnostic tool both clinical practice trials AD.

Language: Английский

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Recognizing Alzheimer's disease from perspective of oligodendrocytes: Phenomena or pathogenesis?

CNS Neuroscience & Therapeutics, Journal Year: 2024, Volume and Issue: 30(3)

Published: March 1, 2024

Abstract Background Accumulation of amyloid beta, tau hyperphosphorylation, and microglia activation are the three highly acknowledged pathological factors Alzheimer's disease (AD). However, oligodendrocytes (OLs) were also widely investigated in pathogenesis treatment for AD. Aims We aimed to update regulatory targets differentiation maturation OLs, emphasized key role OLs occurrence Methods This review first concluded OL with AD pathogenesis, then advanced based on both clinic basic experiments. Later, we extensively discussed possible application current progress diagnosis this complex disease. Results Molecules involving OLs’ or maturation, including various transcriptional factors, cholesterol homeostasis regulators, microRNAs could participate Clinical data point towards impairment patients. Basic research further supports central regulation pathologies. Additionally, classic drugs, donepezil, edaravone, fluoxetine, clemastine demonstrate their potential remedying models, new therapeutics from perspective is constantly being developed. Conclusions believe that dysfunction one important Factors regulating might be biomarkers early agents stimulating warrant development anti‐AD drugs.

Language: Английский

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Behavioral and neuronal extracellular vesicle biomarkers associated with nicotine's enhancement of the reinforcing strength of cocaine in female and male monkeys

Addiction Neuroscience, Journal Year: 2024, Volume and Issue: 11, P. 100151 - 100151

Published: Feb. 15, 2024

While the majority of people with cocaine use disorders (CUD) also co-use tobacco/nicotine, most preclinical research does not include nicotine. The present study examined nicotine and under several conditions intravenous drug self-administration in monkeys, as well potential peripheral biomarkers associated co-use. In Experiment 1, male rhesus monkeys (N=3) self-administered (0.001-0.1 mg/kg/injection) alone (0.01-0.03 a progressive-ratio schedule reinforcement. When was added to cocaine, there significant leftward/upward shift number injections received. 2, socially housed female cynomolgus (N=14) concurrent drug-vs-food choice Adding solution shifted dose-response curves left, more robust shifts noted animals. There no evidence social rank differences. To assess reinforcing strength, delays were presentation drug; required significantly longer decrease choice, compared alone. Blood samples obtained post-session used analyze concentrations neuronally derived small extracellular vesicles (NDE); differences NDE profile observed for kappa-opioid receptors when co-used each controls. These results suggest that interactions involving are simply changing potency, but rather resulting changes strength should be utilized better understand neuropharmacology CUD evaluation treatments.

Language: Английский

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