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.

journal_name

Acta Neuropathol

journal_title

Acta neuropathologica

authors

Fritschi SK,Cintron A,Ye L,Mahler J,Bühler A,Baumann F,Neumann M,Nilsson KP,Hammarström P,Walker LC,Jucker M

doi

10.1007/s00401-014-1339-2

subject

Has Abstract

pub_date

2014-10-01 00:00:00

pages

477-84

issue

4

eissn

0001-6322

issn

1432-0533

journal_volume

128

pub_type

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