Intracerebral Injection of Metal-Binding Domain of Aβ Comprising the Isomerized Asp7 Increases the Amyloid Burden in Transgenic Mice

Intracerebral or intraperitoneal injections of brain extracts from the Alzheimer’s disease patients result in the acceleration of cerebral β-amyloidosis in transgenic mice. Earlier, we have found that intravenous injections of synthetic full-length amyloid-β (Aβ) comprising the isomerized Asp7 trigg...

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Bibliographic Details
Published in:Neurotoxicity research 2016-05, Vol.29 (4), p.551-557
Main Authors: Kulikova, Alexandra A., Cheglakov, Ivan B., Kukharsky, Michail S., Ovchinnikov, Ruslan K., Kozin, Sergey A., Makarov, Alexander A.
Format: Article
Language:English
Subjects:
Alzheimer Disease - genetics
Alzheimer Disease - metabolism
Alzheimer Disease - pathology
Amyloid beta-Peptides - administration & dosage
Amyloid beta-Peptides - metabolism
Amyloid beta-Peptides - pharmacology
Amyloid beta-Protein Precursor - genetics
Amyloidosis - chemically induced
Amyloidosis - genetics
Analysis of Variance
Animals
Aspartic Acid - metabolism
Biomedical and Life Sciences
Biomedicine
Cell Biology
Disease Models, Animal
Gene Expression Regulation - drug effects
Gene Expression Regulation - genetics
Humans
Mice
Mice, Inbred C57BL
Mice, Transgenic
Mutation - genetics
Neurobiology
Neurochemistry
Neurology
Neurosciences
Original Article
Peptide Fragments - administration & dosage
Peptide Fragments - pharmacology
Pharmacology/Toxicology
Plaque, Amyloid - metabolism
Presenilin-1 - genetics
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Description
Summary:Intracerebral or intraperitoneal injections of brain extracts from the Alzheimer’s disease patients result in the acceleration of cerebral β-amyloidosis in transgenic mice. Earlier, we have found that intravenous injections of synthetic full-length amyloid-β (Aβ) comprising the isomerized Asp7 trigger cerebral β-amyloidosis. In vitro studies have shown that isomerization of Asp7 promotes zinc-induced oligomerization of the Aβ metal-binding domain (Aβ 1–16 ). Here we report that single intracerebral injection of the peptide Aβ 1–16 with isomerized Asp7 ( iso Aβ 1–16 ) but not the injection of Aβ 1–16 significantly increases amyloid burden in 5XFAD transgenic mice. Our results provide evidence for a role of iso Aβ 1–16 as a minimal seeding agent of Aβ aggregation in vivo.
ISSN:1029-8428
1476-3524
DOI:10.1007/s12640-016-9603-y