Seeded strain-like transmission of beta-amyloid morphotypes in APP transgenic mice
2013 (English)In: EMBO Reports, ISSN 1469-221X, E-ISSN 1469-3178, Vol. 14, no 11, 1017-1022 p.Article in journal (Refereed) Published
The polymorphic beta-amyloid lesions present in individuals with Alzheimers disease are collectively known as cerebral beta-amyloidosis. Amyloid precursor protein (APP) transgenic mouse models similarly develop beta-amyloid depositions that differ in morphology, binding of amyloid conformation-sensitive dyes, and A beta 40/A beta 42 peptide ratio. To determine the nature of such beta-amyloid morphotypes, beta-amyloid-containing brain extracts from either aged APP23 brains or aged APPPS1 brains were intracerebrally injected into the hippocampus of young APP23 or APPPS1 transgenic mice. APPPS1 brain extract injected into young APP23 mice induced beta-amyloid deposition with the morphological, conformational, and A beta 40/A beta 42 ratio characteristics of beta-amyloid deposits in aged APPPS1 mice, whereas APP23 brain extract injected into young APP23 mice induced b-amyloid deposits with the characteristics of beta-amyloid deposits in aged APP23 mice. Injecting the two extracts into the APPPS1 host revealed a similar difference between the induced beta-amyloid deposits, although less prominent, and the induced deposits were similar to the beta-amyloid deposits found in aged APPPS1 hosts. These results indicate that the molecular composition and conformation of aggregated A beta in APP transgenic mice can be maintained by seeded conversion.
Place, publisher, year, edition, pages
NATURE PUBLISHING GROUP, MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND , 2013. Vol. 14, no 11, 1017-1022 p.
Alzheimer, amyloid, protein aggregation, prion strain
Engineering and Technology
IdentifiersURN: urn:nbn:se:liu:diva-102076DOI: 10.1038/embor.2013.137ISI: 000326389600014OAI: oai:DiVA.org:liu-102076DiVA: diva2:670515
Funding Agencies|BMBF (ERA-Net NEURON-MIPROTRAN)||European Union FP7 HEALTH (LUPAS)||Swedish Foundation for Strategic Research (SSF)||ERC||2013-12-032013-11-292014-04-08