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 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.