Blood neuron-derived exosomes as biomarkers of cognitive impairment in HIV

Sun, Bing; Dalvi, Pranjali; Abadjian, Linda; Tang, Norina; Pulliam, Lynn

doi:10.1097/qad.0000000000001595

Cited by 107 publications

(102 citation statements)

References 54 publications

(56 reference statements)

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“…Firstly, it is important to note that flotillins are universally expressed by all cell types, and consist as a component of all subtypes of extracellular vesicles, independently to their density or size [61]. In addition, it has been indicated that the concentration of plasma neuron-derived exosomes was lower in neurocognitively impaired individuals (regardless of the cause) in comparison with controls [60]. Furthermore, flotillin-1 has been reported to be enriched in exosomes from CSF samples obtained from patients at early stage of severe traumatic brain injury, although no comparisons with control subjects were made in this study [62].…”

Section: Discussion and Future Perspectivesmentioning

confidence: 99%

“…Furthermore, flotillin levels have been found to be negatively correlated with amyloid burden, as shown by the mean cortical PiB retention levels in PiB-PET [10]. However, flotillin-2 levels were shown elevated in brain sections of older non-demented humans compared with younger individuals [41], as well as levels of plasma neuron-derived exosomes were lower in aged HIV-infected individuals compared with controls [60], raising concerns regarding the efficacy of flotillin levels to effectively discriminate between AD and normal ageing. In this regard, flotillin levels were found to remain stable with advancing age in healthy controls in the abovementioned study [10], highlighting the possibility that their levels may not be affected by ageing process itself.…”

Section: Flotillin As a Novel Biomarker Candidate For Ad: Clinical Evmentioning

confidence: 99%

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Flotillin: A Promising Biomarker for Alzheimer’s Disease

Angelopoulou

Paudel

Shaikh

et al. 2020

JPM

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Alzheimer’s disease (AD) is characterized by the accumulation of beta amyloid (Aβ) in extracellular senile plaques and intracellular neurofibrillary tangles (NFTs) mainly consisting of tau protein. Although the exact etiology of the disease remains elusive, accumulating evidence highlights the key role of lipid rafts, as well as the endocytic pathways in amyloidogenic amyloid precursor protein (APP) processing and AD pathogenesis. The combination of reduced Aβ42 levels and increased phosphorylated tau protein levels in the cerebrospinal fluid (CSF) is the most well established biomarker, along with Pittsburgh compound B and positron emission tomography (PiB-PET) for amyloid imaging. However, their invasive nature, the cost, and their availability often limit their use. In this context, an easily detectable marker for AD diagnosis even at preclinical stages is highly needed. Flotillins, being hydrophobic proteins located in lipid rafts of intra- and extracellular vesicles, are mainly involved in signal transduction and membrane–protein interactions. Accumulating evidence highlights the emerging implication of flotillins in AD pathogenesis, by affecting APP endocytosis and processing, Ca2+ homeostasis, mitochondrial dysfunction, neuronal apoptosis, Aβ-induced neurotoxicity, and prion-like spreading of Aβ. Importantly, there is also clinical evidence supporting their potential use as biomarker candidates for AD, due to reduced serum and CSF levels that correlate with amyloid burden in AD patients compared with controls. This review focuses on the emerging preclinical and clinical evidence on the role of flotillins in AD pathogenesis, further addressing their potential usage as disease biomarkers.

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Section: Discussion and Future Perspectivesmentioning

confidence: 99%

Section: Flotillin As a Novel Biomarker Candidate For Ad: Clinical Evmentioning

confidence: 99%

Flotillin: A Promising Biomarker for Alzheimer’s Disease

Angelopoulou

Paudel

Shaikh

et al. 2020

JPM

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“…Dr. Bond’s group recently described a procedure, also using iodixanol velocity gradients, for the effective isolation and separation of exosomes from HIV-1 virions in human plasma (Konadu et al 2016). Dr. Pulliam’s group successfully isolated neuron-derived exosomes from plasma of HIV-infected subjects using precipitation and immunoadsorption with an antibody to a neuronal specific cell surface marker (Sun et al 2017). Additionally, Dr. Hill’s group reported a novel method for the successful enrichment of exosomes from human brain tissue (Vella et al 2017).…”

Section: Resultsmentioning

confidence: 99%

“…More recently, exciting studies have also highlighted alterations in plasma neuron-derived EVs (NDEs) during HIV infection (Sun et al 2017). Intriguingly, in this study, the authors demonstrated that NDEs were influenced by both HIV infection as well as neurocognitive impairment, as evidenced by increased expression of stress proteins such as HMGB1, neurofilament-1, and amyloid beta protein in the NDEs compared with plasma exosomes.…”

Section: Introductionmentioning

confidence: 99%

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Proceedings of the 2017 ISEV symposium on “HIV, NeuroHIV, drug abuse, & EVs”

Yelamanchili

Kashanchi

et al. 2017

J. Neurovirol.

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Despite the success of combination antiretroviral therapy (cART), there is increased prevalence of HIV-associated neurocognitive disorders (HAND) in HIV-1-infected individuals on cART, which poses a major health care challenge. Adding further complexity to this long-term antiretroviral use is the comorbidity with drugs of abuse such as morphine, cocaine, and methamphetamine, which can in turn, exacerbate neurologic and cognitive deficits associated with HAND. Furthermore, HIV proteins, such as the transactivator of transcription (Tat) and the envelope protein (gp120), as well as antiretrovirals themselves can also contribute to the progression of neurodegeneration underlying HAND. In the field of NeuroHIV and drug addiction, EVs hold the potential to serve as biomarkers of cognitive dysfunction, targets of therapy, and as vehicles for therapeutic delivery of agents that can ameliorate disease pathogenesis. Based on the success of a previous Satellite Symposium in 2015 at the ISEV meeting in Washington, experts again expanded on their latest research findings in the field, shedding light on the emerging trends in the field of Extracellular Vesicle (EV) biology in NeuroHIV and drug abuse. The satellite symposium sought to align experts in the fields of NeuroHIV and drug abuse to share their latest insights on the role of EVs in regulating neuroinflammation, neurodegeneration, peripheral immune response, and HIV latency in HIV-infected individuals with or without the comorbidity of drug abuse.

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Isolation of extracellular vesicles from human plasma samples: The importance of controls

Lazaris

Petrillo

Lazaris

et al. 2023

Biotechnology Journal

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Background: Extracellular vesicles (EV) are enriched with proteins and RNA cargo, promoting cell-to-cell communication. Biofluid derived EV cargo is used for discovering disease specific markers for diagnosis and disease monitoring.Rational: Blood is a complex fluid with an abundance of protiens and thus isolation of EVs is challenging. Therefore, methods for EV isolation, including commercial kits use thromboplastin D (TP-D) for pretreatment of plasma to increase EV purity and yield. This pretreatment can introduce contaminants. Method and Results:We performed a comparative study to evaluate the effect of EV isolation methods focusing on (a) pretreatment of plasma with additives, which include: rabbit TP (rTP) versus human recombinant thromboplastin (huTP), to increase purity and yield (b) an additional centrifugation step prior to freezing plasma and (c) comparison of frozen versus fresh plasma EV isolations. Pretreatment with rTP generated a dynamic range of proteins, however, most of these proteins were contaminants, introduced from the rTP (99.1% purity). As an alternative, huTP was used, which did not introduce any significant contaminants, however, this did not increase yield or purity.Additionally, an extra 10,000 g centrifugation did not improve either EV yield or purity.Finally, comparison of fresh or frozen plasma showed no significant difference, an important factor when sourcing plasma from biobanks. Conclusion:Appropriate controlsare required when adding any additives during EV isolation as even a small percentage of contaminants can have a major effect on results. Furthermore, biobanked plasma can be used with no major changes to processing.

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Blood neuron-derived exosomes as biomarkers of cognitive impairment in HIV

Cited by 107 publications

References 54 publications

Flotillin: A Promising Biomarker for Alzheimer’s Disease

Flotillin: A Promising Biomarker for Alzheimer’s Disease

Proceedings of the 2017 ISEV symposium on “HIV, NeuroHIV, drug abuse, & EVs”

Isolation of extracellular vesicles from human plasma samples: The importance of controls

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