title: Aβ seeds resist inactivation by formaldehyde.
abstract: Cerebral β-amyloidosis can be exogenously induced by the intracerebral injection of brain extracts containing aggregated β-amyloid (Aβ) into young, pre-depositing Aβ 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 Aβ itself. Here we report that the β-amyloid-inducing activity of Alzheimer's 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 Aβ are maintained in fixed tissues. The resistance of Aβ 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 Aβ aggregates and the variable clinical features and disease progression of AD even in archived, formalin-fixed autopsy material.
authors.affiliation: German Center for Neurodegenerative Diseases (DZNE), 72076, Tübingen, Germany.
authors.forename: Sarah K
authors.initials: SK
authors.lastname: Fritschi
authors.forename: Amarallys
authors.initials: A
authors.lastname: Cintron
authors.forename: Lan
authors.initials: L
authors.lastname: Ye
authors.forename: Jasmin
authors.initials: J
authors.lastname: Mahler
authors.forename: Anika
authors.initials: A
authors.lastname: Bühler
authors.forename: Frank
authors.initials: F
authors.lastname: Baumann
authors.forename: Manuela
authors.initials: M
authors.lastname: Neumann
authors.forename: K Peter R
authors.initials: KP
authors.lastname: Nilsson
authors.forename: Per
authors.initials: P
authors.lastname: Hammarström
authors.forename: Lary C
authors.initials: LC
authors.lastname: Walker
authors.forename: Mathias
authors.initials: M
authors.lastname: Jucker
mesh_terms: D000367:Age Factors; D000544:Alzheimer Disease / Q000473:pathology*; D016229:Amyloid beta-Peptides / Q000187:drug effects* / Q000378:metabolism / Q000494:pharmacology; D016564:Amyloid beta-Protein Precursor / Q000235:genetics / Q000378:metabolism; D000818:Animals; D001344:Autopsy; D001921:Brain / Q000187:drug effects* / Q000378:metabolism*; D004195:Disease Models, Animal; D005260:Female; D005404:Fixatives / Q000494:pharmacology*; D005557:Formaldehyde / Q000494:pharmacology*; D006801:Humans; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009154:Mutation / Q000235:genetics; D010446:Peptide Fragments / Q000494:pharmacology
chemical_list: D016229:Amyloid beta-Peptides; D016564:Amyloid beta-Protein Precursor; D005404:Fixatives; D010446:Peptide Fragments; C078592:amyloid beta-protein (1-40); D005557:Formaldehyde