Characterization of serum exosomes from a transgenic mouse model of Alzheimer’s disease

Hector Rosas-Hernandez, Elvis Cuevas, James B. Raymick, Bonnie L. Robinson, Syed F. Ali, Joseph Hanig, Sumit Sarkar

Research output: Contribution to journalArticlepeer-review

12 Scopus citations

Abstract

Background: Alzheimer’s Disease (AD) is the most common type of dementia characterized by amyloid plaques containing Amyloid Beta (Aβ) peptides and neurofibrillary tangles containing tau protein. In addition to neuronal loss, Cerebral Amyloid Angiopathy (CAA) commonly occurs in AD. CAA is characterized by Aβ deposition in brain microvessels. Recent studies have suggested that exosomes (cell-derived vesicles containing a diverse cargo) may be involved in the pathogenesis of AD. Objective: Isolate and characterize brain-derived exosomes from a transgenic mouse model of AD that presents CAA. Methods: Exosomes were isolated from serum obtained from 13-month-old wild type and AD transgenic female mice using an exosome precipitation solution. Characterization of exosomal proteins was performed by western blots and dot blots. Results: Serum exosomes were increased in transgenic mice compared to wild types as determined by increased levels of the exosome markers flotillin and alix. High levels of neuronal markers were found in exosomes, without any difference any between the 2 groups. Markers for endothelial-derived exosomes were decreased in the transgenic model, while astrocytic-derived exosomes were increased. Exosome characterization showed increased levels of oligomeric Aβ and oligomeric and monomeric forms tau on the transgenic animals. Levels of amyloid precursor protein were also increased. In addition, pathological and phosphorylated forms of tau were detected, but no difference was observed between the groups. Conclusion: These data suggest that monomeric and oligomeric forms of Aβ and tau are secreted into serum via brain exosomes, most likely derived from astrocytes in the transgenic mouse model of AD with CAA. Studies on the implication of this event in the propagation of AD are underway.

Original languageEnglish (US)
Pages (from-to)388-395
Number of pages8
JournalCurrent Alzheimer Research
Volume16
Issue number5
DOIs
StatePublished - 2019
Externally publishedYes

Keywords

  • Alzheimer’s disease
  • Amyloid beta
  • Amyloid precursor protein
  • Cerebral amyloid angiopathy
  • Exosomes
  • Tau

ASJC Scopus subject areas

  • Neurology
  • Clinical Neurology

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