Proteomics Profiling of Neuron-Derived Small Extracellular Vesicles from Human Plasma: Enabling Single-Subject Analysis

Anastasi, Federica; Masciandaro, Silvia Maria; Carratore, R. Del; Dell’Anno, Maria Teresa; Signore, Giovanni; Falleni, Alessandra; McDonnell, Liam A.; Bongioanni, Paolo

doi:10.3390/ijms22062951

Cited by 47 publications

(32 citation statements)

References 55 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Five studies that did not specifically combine L1CAM and EVs were also removed. A total of 51 articles thus satisfied all criteria (see Figure 1 and list of papers in Table S1 ) ( Anastasi et al, 2021 ; Athauda et al, 2019 ; Bhargava et al, 2021 ; Cha et al, 2019 ; Chawla et al, 2019 ; Cressatti et al, 2021 ; Dagur et al, 2020 ; Eitan et al, 2017 ; Fauré et al, 2006 ; Fu, Jiang, Tofaris, & Davis, 2020 ; Goetzl et al, 2019 ; Goetzl et al, 2015 ; Goetzl, Peltz, Mustapic, Kapogiannis, & Yaffe, 2020 ; Gomes et al, 2015 ; Gu et al, 2020 ; Gutwein et al, 2003 ; Gutwein et al, 2005 ; Herrero et al, 2019 ; Jiang et al, 2020 ; Jiang et al, 2021 ; Keller et al, 2009 ; Kodidela et al, 2020 ; Kumar et al, 2021 ; Mansur et al, 2021 ; Mullins, Mustapic, Goetzl, & Kapogiannis, 2017 ; Nasca et al, 2021 ; Nogueras-Ortiz et al, 2020 ; Norman et al, 2021 ; Pace, Dutt, & Galileo, 2019 ; Patterson, Deep, & Brinkley, 2018 ; Peltz et al, 2020 ; Pulliam, Liston, Sun, & Narvid, 2020 ; Rani et al, 2019 ; Shi et al, 2016 ; Shi et al, 2014 ; Si et al, 2019 ; Stoeck et al, 2006 ; Suire et al, 2017 ; Sun, Dalvi, Abadjian, Tang, & Pulliam, 2017 ; Sun, Fernandes, & Pulliam, 2019 ; Trnka, Ivanova, Hiatt, & Matsell, 2012 ; Walker et al, 2021 ; Webber et al, 2014 ; Winston et al, 2019 ; Winston et al, 2016 ; Winston, Goetzl, Baker, Vitiello, & Rissman, 2018 ; Yang et al, 2009 ; Yang et al, 2011 ; Yuyama et al, 2019 ; …”

Section: Results and Methodsmentioning

confidence: 99%

“…Although this may be appropriate for cell culture experiments, complex EV sources such as blood were used in most investigations. Importantly, several studies [e.g., ( Anastasi et al, 2021 ; Peltz et al, 2020 )] found evidence that non-neuronal materials were present in L1CAM-precipitated material, including broad lipoprotein and free protein contamination ( Anastasi et al, 2021 ). It is thus difficult to assess how non-EV particles and associated molecules might have contributed to the results of previous studies of L1CAM+ EVs.…”

Section: Discussionmentioning

confidence: 99%

“…Interestingly, in this study, miR-9 and miR-451a were also assessed, and the authors concluded that miR-9, a CNS-enriched miRNA, was also enriched in the L1CAM-precipitated material ( Cha et al, 2019 ). Another study amplified miR-155 by qPCR, with normalization to GAPDH mRNA ( Anastasi et al, 2021 ). Finally, one study examined long noncoding RNA by hybridization microarray, followed by validation of one lncRNA by qPCR, with normalization to GAPDH ( Zou et al, 2020 ).…”

Section: Characterization Of L1cam-associated Evsmentioning

confidence: 99%

See 2 more Smart Citations

L1CAM‐associated extracellular vesicles: A systematic review of nomenclature, sources, separation, and characterization

Gomes

Witwer

2022

J of Extracellular Bio

View full text Add to dashboard Cite

When released into biological fluids like blood or saliva, brain extracellular vesicles (EVs) might provide a window into otherwise inaccessible tissue, contributing useful biomarkers of neurodegenerative and other central nervous system (CNS) diseases. To enrich for brain EVs in the periphery, however, cell-specific EV surface markers are needed. The protein that has been used most frequently to obtain EVs of putative neuronal origin is the transmembrane L1 cell adhesion molecule (L1CAM/CD171). In this systematic review, we examine the existing literature on L1CAM and EVs, including investigations of both neurodegenerative disease and cancer through the lens of the minimal information for studies of EVs (MISEV), specifically in the domains of nomenclature usage, EV sources, and EV separation and characterization. Although numerous studies have reported L1CAM-associated biomarker signatures that correlate with disease, interpretation of these results is complicated since L1CAM expression is not restricted to neurons and is also upregulated during cancer progression. A recent study has suggested that L1CAM epitopes are present in biofluids mostly or entirely as cleaved, soluble protein. Our findings on practices and trends in L1CAM-mediated EV separation, enrichment, and characterization yield insights that may assist with interpreting results, evaluating rigor, and suggesting avenues for further exploration.

show abstract

Section: Results and Methodsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Characterization Of L1cam-associated Evsmentioning

confidence: 99%

See 1 more Smart Citation

L1CAM‐associated extracellular vesicles: A systematic review of nomenclature, sources, separation, and characterization

Gomes

Witwer

2022

J of Extracellular Bio

View full text Add to dashboard Cite

show abstract

“…Thus, additional markers may be better suited to identify neuronal (e.g., ATP1A3) or microglial (e.g., LCP1) EVs in CSF ( You et al, 2022 ). L1CAM has been used for the enrichment of neuronal-derived EV from plasma ( Winston et al, 2016 ; Goetzl et al, 2019 ; Pulliam et al, 2019 ; Goetzl et al, 2020 ; Nogueras-Ortiz et al, 2020 ; Anastasi et al, 2021 ; Cressatti et al, 2021 ; Saeedi et al, 2021 ; Yao et al, 2021 ). However, the use of L1CAM as a neuronal EV marker is an ongoing debate in the EV community, in part due to a recent and comprehensive study demonstrated that L1CAM in CSF is not a marker of neuronal EVs ( Norman et al, 2021 ).…”

Section: Discussionmentioning

confidence: 99%

Differential Effects of APOE Genotype on MicroRNA Cargo of Cerebrospinal Fluid Extracellular Vesicles in Females With Alzheimer’s Disease Compared to Males

Sandau

McFarland

Smith

et al. 2022

Front. Cell Dev. Biol.

View full text Add to dashboard Cite

Multiple biological factors, including age, sex, and genetics, influence Alzheimer’s disease (AD) risk. Of the 6.2 million Americans living with Alzheimer’s dementia in 2021, 3.8 million are women and 2.4 million are men. The strongest genetic risk factor for sporadic AD is apolipoprotein E-e4 (APOE-e4). Female APOE-e4 carriers develop AD more frequently than age-matched males and have more brain atrophy and memory loss. Consequently, biomarkers that are sensitive to biological risk factors may improve AD diagnostics and may provide insight into underlying mechanistic changes that could drive disease progression. Here, we have assessed the effects of sex and APOE-e4 on the miRNA cargo of cerebrospinal fluid (CSF) extracellular vesicles (EVs) in AD. We used ultrafiltration (UF) combined with size exclusion chromatography (SEC) to enrich CSF EVs (e.g., Flotillin+). CSF EVs were isolated from female and male AD or controls (CTLs) that were either APOE-e3,4 or -e3,3 positive (n = 7/group, 56 total). MiRNA expression levels were quantified using a custom TaqMan™ array that assayed 190 miRNAs previously found in CSF, including 25 miRNAs that we previously validated as candidate AD biomarkers. We identified changes in the EV miRNA cargo that were affected by both AD and sex. In total, four miRNAs (miR-16-5p, -331-3p, -409-3p, and -454-3p) were significantly increased in AD vs. CTL, independent of sex and APOE-e4 status. Pathway analysis of the predicted gene targets of these four miRNAs with identified pathways was highly relevant to neurodegeneration (e.g., senescence and autophagy). There were also three miRNAs (miR-146b-5p, -150-5p, and -342-3p) that were significantly increased in females vs. males, independent of disease state and APOE-e4 status. We then performed a statistical analysis to assess the effect of APOE genotype in AD within each sex and found that APOE-e4 status affects different subsets of CSF EV miRNAs in females vs. males. Together, this study demonstrates the complexity of the biological factors associated with AD risk and the impact on EV miRNAs, which may contribute to AD pathophysiology.

show abstract

“…In addition, a reduction in miR-155 expression was observed in patients with a higher levodopa dose, suggesting a possible modulatory role of this treatment on miR-155 levels [ 87 ]. Higher expression of miR-155 was also detected in extracellular vesicles derived from neurons of PD patients [ 88 ].…”

Section: Mir-155mentioning

confidence: 99%

MiR-155: An Important Regulator of Neuroinflammation

Zingale

Gugliandolo

Mazzon

2021

IJMS

View full text Add to dashboard Cite

MicroRNAs (miRNAs) are small non-coding RNA molecules that regulate gene expression at the post-transcriptional level and that play an important role in many cellular processes, including modulation of inflammation. MiRNAs are present in high concentrations in the central nervous system (CNS) and are spatially and temporally expressed in a specific way. Therefore, an imbalance in the expression pattern of these small molecules can be involved in the development of neurological diseases. Generally, CNS responds to damage or disease through the activation of an inflammatory response, but many neurological disorders are characterized by uncontrolled neuroinflammation. Many studies support the involvement of miRNAs in the activation or inhibition of inflammatory signaling and in the promotion of uncontrolled neuroinflammation with pathological consequences. MiR-155 is a pro-inflammatory mediator of the CNS and plays an important regulatory role. The purpose of this review is to summarize how miR-155 is regulated and the pathological consequences of its deregulation during neuroinflammatory disorders, including multiple sclerosis, Alzheimer’s disease and other neuroinflammatory disorders. Modulation of miRNAs’ expression could be used as a therapeutic strategy in the treatment of pathological neuroinflammation.

show abstract

Proteomics Profiling of Neuron-Derived Small Extracellular Vesicles from Human Plasma: Enabling Single-Subject Analysis

Cited by 47 publications

References 55 publications

L1CAM‐associated extracellular vesicles: A systematic review of nomenclature, sources, separation, and characterization

L1CAM‐associated extracellular vesicles: A systematic review of nomenclature, sources, separation, and characterization

Differential Effects of APOE Genotype on MicroRNA Cargo of Cerebrospinal Fluid Extracellular Vesicles in Females With Alzheimer’s Disease Compared to Males

MiR-155: An Important Regulator of Neuroinflammation

Contact Info

Product

Resources

About