Plasma microparticles in Alzheimer’s disease: The role of vascular dysfunction

Hosseinzadeh, Soheila; Noroozıan, Maryam; Mortaz, Esmaeil; Mousavizadeh, Kazem

doi:10.1007/s11011-017-0149-3

Cited by 20 publications

(22 citation statements)

References 37 publications

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“…Interestingly, this study did not indicate a difference in EV levels between AD patients and controls. However, a significant difference did appear between AD patients diagnosed with vascular risk factors and those without [ 122 ]. This topic clearly warrants further study, in which EV phenotyping could be expanded to include other surface markers, monitored in different forms of dementias and assessed in longitudinal studies.…”

Section: Brain Ec-derived Evs As Serological Biomarkers For Bbb Statumentioning

confidence: 99%

Extracellular vesicles: mediators and biomarkers of pathology along CNS barriers

Ramirez

Andrews

Paul

et al. 2018

Fluids Barriers CNS

119

108

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Extracellular vesicles (EVs) are heterogeneous, nano-sized vesicles that are shed into the blood and other body fluids, which disperse a variety of bioactive molecules (e.g., protein, mRNA, miRNA, DNA and lipids) to cellular targets over long and short distances. EVs are thought to be produced by nearly every cell type, however this review will focus specifically on EVs that originate from cells at the interface of CNS barriers. Highlighted topics include, EV biogenesis, the production of EVs in response to neuroinflammation, role in intercellular communication and their utility as a therapeutic platform. In this review, novel concepts regarding the use of EVs as biomarkers for BBB status and as facilitators for immune neuroinvasion are also discussed. Future directions and prospective are covered along with important unanswered questions in the field of CNS endothelial EV biology.

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Section: Brain Ec-derived Evs As Serological Biomarkers For Bbb Statumentioning

confidence: 99%

Extracellular vesicles: mediators and biomarkers of pathology along CNS barriers

Ramirez

Andrews

Paul

et al. 2018

Fluids Barriers CNS

119

108

View full text Add to dashboard Cite

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“…Systemic neuronal-derived EVs from AD brains exhibited downregulated mi-RNA (Cha et al, 2019), were increased in number and diameter and a differential protein content (Pulliam et al, 2019). Moreover, endothelial-derived EVs have been found to be increased in AD patients (Hosseinzadeh et al, 2018), which could reflect BBB dysfunction. Moreover, we propose that altered systemic EVs in AD could transfer a variety of proteins that affect NVU homeostasis via the induction of BBB dysfunction and neurotoxicity (Laske et al, 2015;Yang et al, 2018).…”

Section: Introductionmentioning

confidence: 99%

Differential Profile of Systemic Extracellular Vesicles From Sporadic and Familial Alzheimer’s Disease Leads to Neuroglial and Endothelial Cell Degeneration

Villar-Vesga

Henao‐Restrepo

Voshart

et al. 2020

Front. Aging Neurosci.

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Evidence suggests that extracellular vesicles (EVs) act as mediators and biomarkers of neurodegenerative diseases. Two distinct forms of Alzheimer disease (AD) are known: a late-onset sporadic form (SAD) and an early-onset familial form (FAD). Recently, neurovascular dysfunction and altered systemic immunological components have been linked to AD neurodegeneration. Therefore, we characterized systemic-EVs from postmortem SAD and FAD patients and evaluated their effects on neuroglial and endothelial cells. We found increase CLN-5 spots with vesicular morphology in the abluminal portion of vessels from SAD patients. Both forms of AD were associated with larger and more numerous systemic EVs. Specifically, SAD patients showed an increase in endothelial- and leukocyte-derived EVs containing mitochondria; in contrast, FAD patients showed an increase in platelet-derived EVs. We detected a differential protein composition for SAD- and FAD-EVs associated with the coagulation cascade, inflammation, and lipid-carbohydrate metabolism. Using mono- and cocultures (endothelium-astrocytes-neurons) and human cortical organoids, we showed that AD-EVs induced cytotoxicity. Both forms of AD featured decreased neuronal branches area and astrocytic hyperreactivity, but SAD-EVs led to greater endothelial detrimental effects than FAD-EVs. In addition, FAD- and SAD-EVs affected calcium dynamics in a cortical organoid model. Our findings indicate that the phenotype of systemic AD-EVs is differentially defined by the etiopathology of the disease (SAD or FAD), which results in a differential alteration of the NVU cells implied in neurodegeneration.

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“…Inflammation is a key component of conditions such as hypertension, obesity, and diabetes and is associated with the release of biological microparticles into the blood, which may transmit inflammation from one location to another and contribute to the persistence of inflammation locally. Raised blood concentrations of biological microparticles have been found in individuals with Alzheimer's disease [32,33], and their deposition on cerebral vascular endothelium would be expected to lead to inflammation and microbleeds. Such brain microbleeds, forerunners of dementia, have been demonstrated analogously in chronic obstructive pulmonary disease, a condition also associated with generation of microparticles [34,35].…”

Section: Environmental Risk Factors For Dementiamentioning

confidence: 99%

Pollution, Particles, and Dementia: A Hypothetical Causative Pathway

Seaton

Tran

Chen

et al. 2020

IJERPH

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Epidemiological studies of air pollution have shown associations between exposure to particles and dementia. The mechanism of this is unclear. As these seem unlikely in terms of the very small dose likely to reach the brain in usual Western urban circumstances, we extend our 1995 hypothetical explanation of the association of air pollution with cardiac deaths as a plausible alternative explanation of its associations with dementia. Since our original proposal, it has become apparent that inflammation may be carried by blood from organ to organ by biologic microparticles derived from cell membranes. These transmit inflammatory messages to endothelial cells throughout the body as part of a general defensive response to assumed bacterial infection; particulate air pollution has recently been shown to be associated with their release into the blood. We propose that episodic release of biologic microparticles from pollution-induced lung inflammation causes secondary inflammation in the blood-brain barrier and cerebral microbleeds, culminating over time in cognitive impairment. Ultimately, by incomplete repair and accumulation of amyloid, this increases the risk of Alzheimer’s disease. Importantly, this mechanism may also explain the relationships of other inflammatory conditions and environmental factors with cognitive decline, and point to new opportunities to understand and prevent dementia.

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Plasma microparticles in Alzheimer’s disease: The role of vascular dysfunction

Cited by 20 publications

References 37 publications

Extracellular vesicles: mediators and biomarkers of pathology along CNS barriers

Extracellular vesicles: mediators and biomarkers of pathology along CNS barriers

Differential Profile of Systemic Extracellular Vesicles From Sporadic and Familial Alzheimer’s Disease Leads to Neuroglial and Endothelial Cell Degeneration

Pollution, Particles, and Dementia: A Hypothetical Causative Pathway

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