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A? seeds resist inactivation by formaldehyde.

ABSTRACT: Cerebral ?-amyloidosis can be exogenously induced by the intracerebral injection of brain extracts containing aggregated ?-amyloid (A?) into young, pre-depositing A? 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? itself. Here we report that the ?-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 A? are maintained in fixed tissues. The resistance of A? 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? aggregates and the variable clinical features and disease progression of AD even in archived, formalin-fixed autopsy material.

SUBMITTER: Fritschi SK

PROVIDER: S-EPMC4169116 | biostudies-literature | 2014 Oct

REPOSITORIES: biostudies-literature

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Aβ seeds resist inactivation by formaldehyde.

Fritschi Sarah K SK Cintron Amarallys A Ye Lan L Mahler Jasmin J Bühler Anika A Baumann Frank F Neumann Manuela M Nilsson K Peter R KP Hammarström Per P Walker Lary C LC Jucker Mathias M

Acta neuropathologica 20140906 4

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 w ...[more]

PMID: 25193240

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A? seeds resist inactivation by formaldehyde.

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Aβ seeds resist inactivation by formaldehyde.

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