title: 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.
authors: Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, Vavilov Street 32, Moscow, Russia, 119991. kulikovaaa@gmail.com.
authors: Alexandra A
authors: AA
authors: Kulikova
authors: Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, Vavilov Street 32, Moscow, Russia, 119991.
authors: Ivan B
authors: IB
authors: Cheglakov
authors: School of Biosciences, Cardiff University, Museum Avenue, Cardiff, UK.|Institute of Physiologically Active Compounds, Russian Academy of Sciences, Severniy Proezd, Chernogolovka, Moscow region, Russia, 1142432.
authors: Michail S
authors: MS
authors: Kukharsky
authors: Institute of Physiologically Active Compounds, Russian Academy of Sciences, Severniy Proezd, Chernogolovka, Moscow region, Russia, 1142432.
authors: Ruslan K
authors: RK
authors: Ovchinnikov
authors: Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, Vavilov Street 32, Moscow, Russia, 119991. kozinsa@gmail.com.
authors: Sergey A
authors: SA
authors: Kozin
authors: Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, Vavilov Street 32, Moscow, Russia, 119991.
authors: Alexander A
authors: AA
authors: Makarov
mesh_terms: D000544:Alzheimer Disease / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D016229:Amyloid beta-Peptides / Q000008:administration & dosage / Q000378:metabolism* / Q000494:pharmacology*; D016564:Amyloid beta-Protein Precursor / Q000235:genetics; D000686:Amyloidosis / Q000139:chemically induced* / Q000235:genetics; D000704:Analysis of Variance; D000818:Animals; D001224:Aspartic Acid / Q000378:metabolism*; D004195:Disease Models, Animal; D005786:Gene Expression Regulation / Q000187:drug effects / Q000235:genetics; D006801:Humans; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009154:Mutation / Q000235:genetics; D010446:Peptide Fragments / Q000008:administration & dosage / Q000494:pharmacology*; D058225:Plaque, Amyloid / Q000378:metabolism*; D053764:Presenilin-1 / Q000235:genetics
chemical_list: D016229:Amyloid beta-Peptides; D016564:Amyloid beta-Protein Precursor; C508853:PSEN1 protein, human; D010446:Peptide Fragments; D053764:Presenilin-1; C433241:amyloid beta-protein (1-16); D001224:Aspartic Acid
keywords: Aggregation; Alzheimer’s disease; Amyloid-β; Metal-binding domain; Seeding; β-Amyloidosis