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Brain Exosomes: Friend or Foe in Alzheimer’s Disease?

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Abstract

Alzheimer’s disease (AD) is the most common neurodegenerative disease. It is known to be a multifactorial disease and several causes are associated with its occurrence as well as progression. However, the accumulation of amyloid beta (Aβ) is widely considered its major pathogenic hallmark. Additionally, neurofibrillary tangles (NFT), mitochondrial dysfunction, oxidative stress, and aging (cellular senescence) are considered as additional hits affecting the disease pathology. Several studies are now suggesting important role of inflammation in AD, which shifts our thought towards the brain’s resident immune cells, microglia, and astrocytes; how they interact with neurons; and how these interactions are affected by intra and extracellular stressful factors. These interactions can be modulated by different mechanisms and pathways, in which exosomes could play an important role. Exosomes are multivesicular bodies secreted by nearly all types of cells. The exosomes secreted by glial cells or neurons affect the interactions and thus the physiology of these cells by transmitting miRNAs, proteins, and lipids. Exosomes can serve as a friend or foe to the neuron function, depending upon the carried signals. Exosomes, from the healthy microenvironment, may assist neuron function and health, whereas, from the stressed microenvironment, they carry oxidative and inflammatory signals to the neurons and thus prove detrimental to the neuronal function. Furthermore, exosomes can cross the blood–brain barrier (BBB), and from the blood plasma they can enter the brain cells and activate microglia and astrocytes. Exosomes can transport Aβ or Tau, cytokines, miRNAs between the cells, and alter the physiology of recipient cells. They can also assist in Aβ clearance and regulation of synaptic activity. The exosomes derived from different cells play different roles, and this field is still in its infancy stage. This review advocates exosomes’ role as a friend or foe in neurodegenerative diseases, especially in the case of Alzheimer’s disease.

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Acknowledgements

H.V. and S.K. acknowledges financial support in the form of a junior/senior research fellowship (JRF/SRF) from the University Grants Commission and Council for Scientific and Industrial Research (CSIR), Govt. of India, New Delhi, India, respectively. Because of the limited focus of the article, many relevant and appropriate references could not be included, for which the authors apologize.

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  1. Monisha Dhiman

    Present address: Department of Microbiology, School of Biological Sciences , Central University of Punjab, Bathinda, Punjab, India

Authors and Affiliations

  1. Department of Microbiology, School of Biological Sciences , Central University of Punjab, Bathinda, Punjab, India

    Sharanjot Kaur

  2. Department of Zoology, School of Biological Sciences, Central University of Punjab, Village Ghudda151 401, Punjab, Bathinda, India

    Harkomal Verma & Anil K. Mantha

  3. Department of Medicine, University of Udine, Udine, Italy

    Gianluca Tell & Gian Luigi Gigli

  4. Clinical Neurology, Udine University Hospital, Udine, Italy

    Gian Luigi Gigli & Francesco Janes

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AKM conceived the idea of the manuscript. SK and HV performed literature review and wrote the manuscript. MD made the outline of the draft. SK and HV made figures and table. GT, GLG, and FJ critically reviewed the manuscript and helped in revising it. All authors have read the manuscript and agreed to the final draft of the manuscript.

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Correspondence to Anil K. Mantha.

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Sharanjot Kaur and Harkomal Verma:  These authors contributed equally to the work

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Kaur, S., Verma, H., Dhiman, M. et al. Brain Exosomes: Friend or Foe in Alzheimer’s Disease?. Mol Neurobiol 58, 6610–6624 (2021). https://doi.org/10.1007/s12035-021-02547-y

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