Pre-plaque conformational changes in Alzheimer's disease-linked Aβ and APP

Forskningsoutput: TidskriftsbidragArtikel i vetenskaplig tidskrift

Abstract

Reducing levels of the aggregation-prone Aβ peptide that accumulates in the brain with Alzheimer's disease (AD) has been a major target of experimental therapies. An alternative approach may be to stabilize the physiological conformation of Aβ. To date, the physiological state of Aβ in brain remains unclear, since the available methods used to process brain tissue for determination of Aβ aggregate conformation can in themselves alter the structure and/or composition of the aggregates. Here, using synchrotron-based Fourier transform infrared micro-spectroscopy, non-denaturing gel electrophoresis and conformational specific antibodies we show that the physiological conformations of Aβ and amyloid precursor protein (APP) in brain of transgenic mouse models of AD are altered before formation of amyloid plaques. Furthermore, focal Aβ aggregates in brain that precede amyloid plaque formation localize to synaptic terminals. These changes in the states of Aβ and APP that occur prior to plaque formation may provide novel targets for AD therapy.

Detaljer

Författare
Enheter & grupper
Externa organisationer
  • Autonomous University of Barcelona
Forskningsområden

Ämnesklassifikation (UKÄ) – OBLIGATORISK

  • Neurovetenskaper
Originalspråkengelska
Artikelnummer14726
TidskriftNature Communications
Volym8
StatusPublished - 2017 mar 13
PublikationskategoriForskning
Peer review utfördJa

Relaterad forskningsoutput

Willén, K., 2017, Lund: Lund University, Faculty of Medicine. 80 s.

Forskningsoutput: AvhandlingDoktorsavhandling (sammanläggning)

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