Transmission of cerebral amyloid pathology by peripheral administration of misfolded Aβ aggregates

Mol Psychiatry. 2021 Oct;26(10):5690-5701. doi: 10.1038/s41380-021-01150-w. Epub 2021 May 17.

Abstract

Previous reports showed that brain Aβ amyloidosis can be induced in animal models by exogenous administration of pre-formed aggregates. To date, only intra-peritoneal and intra-venous administrations are described as effective means to peripherally accelerate brain Aβ amyloidosis by seeding. Here, we show that cerebral accumulation of Aβ can be accelerated after exposing mouse models of Alzheimer's disease (AD) to Aβ seeds by different peripheral routes of administration, including intra-peritoneal and intra-muscular. Interestingly, animals receiving drops of brain homogenate laden with Aβ seeds in the eyes were efficiently induced. On the contrary, oral administration of large quantities of brain extracts from aged transgenic mice and AD patients did not have any effect in brain pathology. Importantly, pathological induction by peripheral administration of Aβ seeds generated a large proportion of aggregates in blood vessels, suggesting vascular transport. This information highlights the role of peripheral tissues and body fluids in AD-related pathological changes.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alzheimer Disease*
  • Amyloid beta-Peptides / metabolism
  • Amyloid beta-Protein Precursor
  • Amyloidosis*
  • Animals
  • Brain / metabolism
  • Disease Models, Animal
  • Humans
  • Mice
  • Mice, Transgenic
  • Plaque, Amyloid

Substances

  • Amyloid beta-Peptides
  • Amyloid beta-Protein Precursor