A beta seeds resist inactivation by formaldehyde

Fritschi, Sarah K.German Centre Neurodegenerat Disease DZNE, Germany; University of Tubingen, Germany; University of Tubingen, Germany (författare)

Funding Agencies|Competence Network on Degenerative Dementias [BMBF-01GI0705]; National Institutes of Health [R21AG040589, P51RR165, P51OD11132, R36AG043646]; MetLife Foundation; Swedish Research Council
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.

Cintron, AmarallysEmory University, GA 30329 USA (författare)
Ye, LanGerman Centre Neurodegenerat Disease DZNE, Germany; University of Tubingen, Germany; University of Tubingen, Germany (författare)
Mahler, JasminGerman Centre Neurodegenerat Disease DZNE, Germany; University of Tubingen, Germany; University of Tubingen, Germany (författare)
Buehler, AnikaGerman Centre Neurodegenerat Disease DZNE, Germany; University of Tubingen, Germany (författare)
Baumann, FrankGerman Centre Neurodegenerat Disease DZNE, Germany; University of Tubingen, Germany (författare)
Neumann, ManuelaGerman Centre Neurodegenerat Disease DZNE, Germany; University of Tubingen, Germany (författare)
Nilsson, PeterLinköpings universitet,Kemi,Tekniska högskolan(Swepub:liu)petni61 (författare)
Hammarström, PerLinköpings universitet,Kemi,Tekniska högskolan(Swepub:liu)perha81 (författare)
Walker, Lary C.Emory University, GA 30329 USA; Emory University, GA 30322 USA (författare)
Jucker, MathiasGerman Centre Neurodegenerat Disease DZNE, Germany; University of Tubingen, Germany (författare)
German Centre Neurodegenerat Disease DZNE, Germany; University of Tubingen, Germany; University of Tubingen, GermanyEmory University, GA 30329 USA (creator_code:org_t)

Ingår i:Acta Neuropathologica: Springer Verlag (Germany)128:4, s. 477-4840001-63221432-0533

Av författaren/redakt...: Fritschi, Sarah ...; Cintron, Amarall ...; Ye, Lan; Mahler, Jasmin; Buehler, Anika; Baumann, Frank; visa fler...; Neumann, Manuela; Nilsson, Peter; Hammarström, Per; Walker, Lary C.; Jucker, Mathias; visa färre...

Om ämnet

Kungliga biblioteket hanterar dina personuppgifter i enlighet med EU:s dataskyddsförordning (2018), GDPR. Läs mer om hur det funkar här.
Så här hanterar KB dina uppgifter vid användning av denna tjänst.