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

Abstract:

: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 (Aβ1-16). Here we report that single intracerebral injection of the peptide Aβ1-16 with isomerized Asp7 (isoAβ1-16) but not the injection of Aβ1-16 significantly increases amyloid burden in 5XFAD transgenic mice. Our results provide evidence for a role of isoAβ1-16 as a minimal seeding agent of Aβ aggregation in vivo.

journal_name

Neurotox Res

journal_title

Neurotoxicity research

authors

Kulikova AA,Cheglakov IB,Kukharsky MS,Ovchinnikov RK,Kozin SA,Makarov AA

doi

10.1007/s12640-016-9603-y

subject

Has Abstract

pub_date

2016-05-01 00:00:00

pages

551-7

issue

4

eissn

1029-8428

issn

1476-3524

pii

10.1007/s12640-016-9603-y

journal_volume

29

pub_type

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