Multiple factors contribute to the peripheral induction of cerebral β-amyloidosis.

Abstract

Deposition of aggregated amyloid-β (Aβ) peptide in brain is an early event and hallmark pathology of Alzheimer's disease and cerebral Aβ angiopathy. Experimental evidence supports the concept that Aβ multimers can act as seeds and structurally corrupt other Aβ peptides by a self-propagating mechanism. Here we compare the induction of cerebral β-amyloidosis by intraperitoneal applications of Aβ-containing brain extracts in three Aβ-precursor protein (APP) transgenic mouse lines that differ in levels of transgene expression in brain and periphery (APP23 mice, APP23 mice lacking murine APP, and R1.40 mice). Results revealed that beta-amyloidosis induction, which could be blocked with an anti-Aβ antibody, was dependent on the amount of inoculated brain extract and on the level of APP/Aβ expression in the brain but not in the periphery. The induced Aβ deposits in brain occurred in a characteristic pattern consistent with the entry of Aβ seeds at multiple brain locations. Intraperitoneally injected Aβ could be detected in blood monocytes and some peripheral tissues (liver, spleen) up to 30 d after the injection but escaped histological and biochemical detection thereafter. These results suggest that intraperitoneally inoculated Aβ seeds are transported from the periphery to the brain in which corruptive templating of host Aβ occurs at multiple sites, most efficiently in regions with high availability of soluble Aβ.

• Authors: Yvonne S Eisele, Sarah K Fritschi, Tsuyoshi Hamaguchi, Ulrike Obermüller, Petra Füger, Angelos Skodras, Claudia Schäfer, Jörg Odenthal, Mathias Heikenwalder, Matthias Staufenbiel, Mathias Jucker
• Journal: The Journal of neuroscience : the official journal of the Society for Neuroscience (J Neurosci) Vol. 34 Issue 31 Pg. 10264-73 (Jul 30 2014) ISSN: 1529-2401 [Electronic] United States
• PMID: 25080588 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2014 the authors 0270-6474/14/3410264-10$15.00/0.

Chemical References

• Amyloid beta-Peptides
• Amyloid beta-Protein Precursor
• Antibodies

Topics

• Amyloid beta-Peptides (immunology, metabolism, toxicity)
• Amyloid beta-Protein Precursor (genetics)
• Amyloidosis (chemically induced, genetics, pathology)
• Animals
• Antibodies (pharmacology)
• Blood Cells (metabolism, pathology)
• Cerebral Cortex (drug effects, metabolism, pathology)
• Dose-Response Relationship, Drug
• Drug Administration Routes
• Female
• Humans
• Male
• Mice
• Mice, Inbred C57BL
• Mice, Transgenic
• Mutation (genetics)
• Peritoneal Cavity (pathology)
• Plaque, Amyloid (pathology)
• Time Factors