Exosomes in Alzheimer’s Disease: Potential Role as Pathological Mediators, Biomarkers and Therapeutic Targets

Lakshmi, Sreeja; Essa, Musthafa Mohamed; Hartman, Richard E.; Guillemin, Gilles J.; Sivan, Sureshkumar; Elumalai, Preetham

doi:10.1007/s11064-020-03111-1

Cited by 29 publications

(20 citation statements)

References 61 publications

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“…Several other groups claimed that Aβ seeds could be transported via axons (Clavaguera et al, 2014;Guo and Lee, 2014;Boluda et al, 2015;Ye et al, 2015). In addition, the levels of Aβ 42 in the peripheral blood neuronal-derived exosomes in AD patients were higher than those in aMCI and healthy people, indicating that exosomes could also act as transport vehicles for Aβ 42 (Jia et al, 2019;Lakshmi et al, 2020). Altogether, neurons, axons, neuronal-derived exosomes, and peripheral monocytes can be used as potential carriers of Aβ 42 delivery, and there is currently evidence supporting axonal transport as a critical mode of disease propagation within the nervous system.…”

Section: Discussionmentioning

confidence: 99%

Dynamic Changes in the Levels of Amyloid-β42 Species in the Brain and Periphery of APP/PS1 Mice and Their Significance for Alzheimer’s Disease

Zhang

Yang

et al. 2021

Front. Mol. Neurosci.

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Although amyloid-β42 (Aβ42) has been used as one of the core biomarkers for Alzheimer’s disease (AD) diagnosis, the dynamic changes of its different forms in the brain, blood, and even intestines and its correlation with the progression of AD disease remain obscure. Herein, we screened Aβ42-specific preferred antibody pairs 1F12/1F12 and 1F12/2C6 to accurately detect Aβ42 types using sandwich ELISA, including total Aβ42, Aβ42 oligomers (Aβ42Os), and Aβ42 monomers (Aβ42Ms). The levels of Aβ42 species in the brain, blood, and intestines of different aged APP/PS1 mice were quantified to study their correlation with AD progression. Total Aβ42 levels in the blood were not correlated with AD progression, but Aβ42Ms level in the blood of 9-month-old APP/PS1 mice was significantly reduced, and Aβ42Os level in the brain was significantly elevated compared to 3-month-old APP/PS1, demonstrating that the levels of Aβ42Ms and Aβ42Os in the blood and brain were correlated with AD progression. Interestingly, in 9-month-old APP/PS1 mice, the level of Aβ42 in the intestine was higher than that in 3-month-old APP/PS1 mice, indicating that the increased level of Aβ42 in the gastrointestinal organs may also be related to the progression of AD. Meanwhile, changes in the gut microbiota composition of APP/PS1 mice with age were also observed. Therefore, the increase in Aβ derived from intestinal tissues and changes in microbiome composition can be used as a potential early diagnosis tool for AD, and further used as an indicator of drug intervention to reduce brain amyloid.

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Section: Discussionmentioning

confidence: 99%

Dynamic Changes in the Levels of Amyloid-β42 Species in the Brain and Periphery of APP/PS1 Mice and Their Significance for Alzheimer’s Disease

Zhang

Yang

et al. 2021

Front. Mol. Neurosci.

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“…Figure 1 illustrates how EXOs can carry Aβ oligomers and tau protein, whose accumulation is responsible for causing AD [ 21 , 22 ]. Aβ is the principal component of amyloid plaques, extracellular deposits detected in AD patients’ brains.…”

Section: Exosomes As a Player In Ad Pathogenesismentioning

confidence: 99%

Exosomes in Alzheimer’s Disease: From Being Pathological Players to Potential Diagnostics and Therapeutics

Soliman

Ghonaim

Gharib

et al. 2021

IJMS

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Exosomes (EXOs) were given attention as an extracellular vesicle (EV) with a pivotal pathophysiological role in the development of certain neurodegenerative disorders (NDD), such as Parkinson’s and Alzheimer’s disease (AD). EXOs have shown the potential to carry pathological and therapeutic cargo; thus, researchers have harnessed EXOs in drug delivery applications. EXOs have shown low immunogenicity as natural drug delivery vehicles, thus ensuring efficient drug delivery without causing significant adverse reactions. Recently, EXOs provided potential drug delivery opportunities in AD and promising future clinical applications with the diagnosis of NDD and were studied for their usefulness in disease detection and prediction prior to the emergence of symptoms. In the future, the microfluidics technique will play an essential role in isolating and detecting EXOs to diagnose AD before the development of advanced symptoms. This review is not reiterative literature but will discuss why EXOs have strong potential in treating AD and how they can be used as a tool to predict and diagnose this disorder.

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“…This high structural stability prevents the degradation of circulating biomarkers and reflects the intra‐neuronal condition in the periphery. The application of blood EV proteins as disease biomarkers have rapidly proliferates in multiple aspects of medical diseases, including cancer, 10 cardiovascular diseases, 11 and AD 12 …”

Section: Introductionmentioning

confidence: 99%

Plasma extracellular vesicles tau and β‐amyloid as biomarkers of cognitive dysfunction of Parkinson's disease

et al. 2021

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The contribution of circulatory tau and β‐amyloid in Parkinson's disease (PD), especially the cognitive function, remains inconclusive. Extracellular vesicles (EVs) cargo these proteins throughout the bloodstream after they are directly secreted from many cells, including neurons. The present study aims to investigate the role of the plasma EV‐borne tau and β‐amyloid as biomarkers for cognitive dysfunction in PD by investigating subjects with mild to moderate stage of PD (n = 116) and non‐PD controls (n = 46). Plasma EVs were isolated, and immunomagnetic reduction‐based immunoassay was used to assess the levels of α‐synuclein, tau, and β‐amyloid 1‐42 (Aβ1‐42) within the EVs. Artificial neural network (ANN) models were then applied to predict cognitive dysfunction. We observed no significant difference in plasma EV tau and Aβ1‐42 between PD patients and controls. Plasma EV tau was significantly associated with cognitive function. Moreover, plasma EV tau and Aβ1‐42 were significantly elevated in PD patients with cognitive impairment when compared to PD patients with optimal cognition. The ANN model used the plasma EV α‐synuclein, tau, and Aβ1‐42, as well as the patient's age and gender, as predicting factors. The model achieved an accuracy of 91.3% in identifying cognitive dysfunction in PD patients, and plasma EV tau and Aβ1‐42 are the most valuable factors. In conclusion, plasma EV tau and Aβ1‐42 are significant markers of cognitive function in PD patients. Combining with the plasma EV α‐synuclein, age, and sex, plasma EV tau and Aβ1‐42 can identify cognitive dysfunction in PD patients. This study corroborates the prognostic roles of plasma EV tau and Aβ1‐42 in PD.

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Exosomes in Alzheimer’s Disease: Potential Role as Pathological Mediators, Biomarkers and Therapeutic Targets

Cited by 29 publications

References 61 publications

Dynamic Changes in the Levels of Amyloid-β42 Species in the Brain and Periphery of APP/PS1 Mice and Their Significance for Alzheimer’s Disease

Dynamic Changes in the Levels of Amyloid-β42 Species in the Brain and Periphery of APP/PS1 Mice and Their Significance for Alzheimer’s Disease

Exosomes in Alzheimer’s Disease: From Being Pathological Players to Potential Diagnostics and Therapeutics

Plasma extracellular vesicles tau and β‐amyloid as biomarkers of cognitive dysfunction of Parkinson's disease

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