A beta seeds resist inactivation by formaldehyde
2014 (English)In: Acta Neuropathologica, ISSN 0001-6322, E-ISSN 1432-0533, Vol. 128, no 4, 477-484 p.Article in journal (Refereed) Published
Cerebral beta-amyloidosis can be exogenously induced by the intracerebral injection of brain extracts containing aggregated beta-amyloid (A beta) into young, pre-depositing A beta precursor protein- (APP) transgenic mice. Previous work has shown that the induction involves a prion-like seeding mechanism in which the seeding agent is aggregated A beta itself. Here we report that the beta-amyloid-inducing activity of Alzheimers disease (AD) brain tissue or aged APP-transgenic mouse brain tissue is preserved, albeit with reduced efficacy, after formaldehyde fixation. Moreover, spectral analysis with amyloid conformation-sensitive luminescent conjugated oligothiophene dyes reveals that the strain-like properties of aggregated A beta are maintained in fixed tissues. The resistance of A beta seeds to inactivation and structural modification by formaldehyde underscores their remarkable durability, which in turn may contribute to their persistence and spread within the body. The present findings can be exploited to establish the relationship between the molecular structure of A beta aggregates and the variable clinical features and disease progression of AD even in archived, formalin-fixed autopsy material.
Place, publisher, year, edition, pages
Springer Verlag (Germany) , 2014. Vol. 128, no 4, 477-484 p.
Amyloid; Alzheimer; Prion; Fixation; Strain
IdentifiersURN: urn:nbn:se:liu:diva-111439DOI: 10.1007/s00401-014-1339-2ISI: 000341906600002PubMedID: 25193240OAI: oai:DiVA.org:liu-111439DiVA: diva2:757316
Funding Agencies|Competence Network on Degenerative Dementias [BMBF-01GI0705]; National Institutes of Health [R21AG040589, P51RR165, P51OD11132, R36AG043646]; MetLife Foundation; Swedish Research Council2014-10-212014-10-172014-10-21