In situ structural characterization of early amyloid aggregates in Alzheimer’s disease transgenic mice and Octodon degus

Forskningsoutput: TidskriftsbidragArtikel i vetenskaplig tidskrift

Abstract

Amyloid plaques composed of Aβ amyloid peptides and neurofibrillary tangles are a pathological hallmark of Alzheimer’s disease. In situ identification of early-stage amyloid aggregates in Alzheimer’s disease is relevant for their importance as potential targets for effective drugs. Synchrotron-based infrared imaging is here used to identify early-stage oligomeric/granular aggregated amyloid species in situ in the brain of APP/PS1 transgenic mice and Octodon degus for the first time. Also, APP/PS1 mice show fibrillary aggregates at 6 and 12 months whereas very little formation of fibrils is found in aged Octodon degus. Finally, significant decreased burden of early-stage aggregates and fibrillary aggregates is obtained following treatment with G4-His-Mal dendrimers (a neurodegenerative protector) in 6-month-old APP/PS1 mice, thus demonstrating putative therapeutic properties of G4-His-Mal dendrimers in AD models. Identification, localization, and characterization using infrared imaging of these non-fibrillary species in the cerebral cortex at early stages of AD progression in transgenic mice point to their relevance as putative pharmacological targets. No less important, early detection of these structures may be useful in the search for markers for non-invasive diagnostic techniques.

Detaljer

Författare
  • Núria Benseny-Cases
  • Elena Álvarez-Marimon
  • Ester Aso
  • Margarita Carmona
  • Oxana Klementieva
  • Dietmar Appelhans
  • Isidre Ferrer
  • Josep Cladera
Enheter & grupper
Externa organisationer
  • Autonomous University of Barcelona
  • University of Barcelona
  • Leibniz Institute of Polymer Research, Dresden
  • ALBA Synchrotron Light Facility
  • L'Hospitalet de Llobregat, Barcelona
  • CIBER Enfermedades Neurodegenerativas (CIBERNED)
Forskningsområden

Ämnesklassifikation (UKÄ) – OBLIGATORISK

  • Neurovetenskaper
Originalspråkengelska
Artikelnummer5888
TidskriftScientific Reports
Volym10
Utgåva nummer1
StatusPublished - 2020
PublikationskategoriForskning
Peer review utfördJa