A highly insoluble state of Aβ similar to that of Alzheimers disease brain is found in Arctic APP transgenic mice
2009 (English)In: Neurobiology of Aging, ISSN 0197-4580, Vol. 30, no 9, 1393-1405 p.Article in journal (Refereed) Published
Amyloid-β (Aβ) is a major drug target in Alzheimers disease. Here, we demonstrate that deposited Aβ is SDS insoluble in tgAPP-ArcSwe, a transgenic mouse model harboring the Arctic (E693G) and Swedish (KM670/671NL) APP mutations. Formic acid was needed to extract the majority of deposited Aβ in both tgAPP-ArcSwe and Alzheimers disease brain, but not in a commonly used type of mouse model with the Swedish mutation alone. Interestingly, the insoluble state of Arctic Aβ was determined early on and did not gradually evolve with time. In tgAPP-ArcSwe, Aβ plaques displayed a patchy morphology with bundles of Aβ fibrils, whereas amyloid cores in tgAPP-Swe were circular with radiating fibrils. Amyloid was more densely stacked in tgAPP-ArcSwe, as demonstrated with a conformation sensitive probe. A reduced increase in plasma Aβ was observed following acute administration of an Aβ antibody in tgAPP-ArcSwe, results that might imply reduced brain to plasma Aβ efflux. TgAPP-ArcSwe, with its insoluble state of deposited Aβ, could serve as a complementary model to better predict the outcome of clinical trials.
Place, publisher, year, edition, pages
2009. Vol. 30, no 9, 1393-1405 p.
ABeta-peptide; Alzheimers disease; Amyloid beta; Immunotherapy; Solubility; Transgenic
Medical and Health Sciences
IdentifiersURN: urn:nbn:se:liu:diva-21240DOI: 10.1016/j.neurobiolaging.2007.11.022OAI: oai:DiVA.org:liu-21240DiVA: diva2:240988