Emerging Roles of Extracellular Vesicles in Alzheimer's Disease: Focus on Synaptic Dysfunction and Vesicle-Neuron Interaction

Cells. 2022 Dec 23;12(1):63. doi: 10.3390/cells12010063.

Abstract

Alzheimer's disease (AD) is considered by many to be a synaptic failure. Synaptic function is in fact deeply affected in the very early disease phases and recognized as the main cause of AD-related cognitive impairment. While the reciprocal involvement of amyloid beta (Aβ) and tau peptides in these processes is under intense investigation, the crucial role of extracellular vesicles (EVs) released by different brain cells as vehicles for these molecules and as mediators of early synaptic alterations is gaining more and more ground in the field. In this review, we will summarize the current literature on the contribution of EVs derived from distinct brain cells to neuronal alterations and build a working model for EV-mediated propagation of synaptic dysfunction in early AD. A deeper understanding of EV-neuron interaction will provide useful targets for the development of novel therapeutic approaches aimed at hampering AD progression.

Keywords: Alzheimer’s disease; beta amyloid; extracellular vesicles; extracellular vesicle–neuron interaction; synaptic dysfunction; tau protein.

Publication types

  • Review
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alzheimer Disease*
  • Amyloid beta-Peptides / metabolism
  • Brain / metabolism
  • Extracellular Vesicles* / metabolism
  • Humans
  • Neurons / metabolism

Substances

  • Amyloid beta-Peptides

Grants and funding

This work was supported by the Ministry of University and Research-PNRR project n. (T.H.E.) ECS_00000017 to N.O., Alzheimer’s Association Research Fellowship (AARF) 2018-AARF-588984, and the Italian Ministry of Health (RF-2018-12365333) to C.V.