Aβ seeds resist inactivation by formaldehyde
| Autor: | Lary C. Walker, Jasmin Mahler, Mathias Jucker, Manuela Neumann, K. Peter R. Nilsson, Amarallys F. Cintron, Sarah K. Fritschi, Per Hammarström, Anika Bühler, Lan Ye, Frank Baumann |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2014 |
| Předmět: |
medicine.disease_cause
chemistry.chemical_compound pathology [Alzheimer Disease] Mice Amyloid beta-Protein Precursor metabolism [Amyloid beta-Protein Precursor] Spectral analysis Mutation Age Factors Brain Biochemistry genetics [Amyloid beta-Protein Precursor] pharmacology [Peptide Fragments] drug effects [Brain] Female Autopsy Alzheimer's disease Genetically modified mouse Amyloid Transgene Formaldehyde metabolism [Amyloid beta-Peptides] Mice Transgenic genetics [Mutation] Biology Article Pathology and Forensic Medicine Cellular and Molecular Neuroscience Fixatives Alzheimer Disease pharmacology [Formaldehyde] medicine Animals Humans ddc:610 Amyloid beta-Peptides Disease progression amyloid beta-protein (1-40) drug effects [Amyloid beta-Peptides] medicine.disease Peptide Fragments Mice Inbred C57BL Disease Models Animal chemistry metabolism [Brain] pharmacology [Amyloid beta-Peptides] Biophysics Neurology (clinical) pharmacology [Fixatives] |
| Zdroj: | Acta neuropathologica 128(4), 477-484 (2014). doi:10.1007/s00401-014-1339-2 |
| DOI: | 10.1007/s00401-014-1339-2 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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