Seeded strain-like transmission of β-amyloid morphotypes in APP transgenic mice

摘要

The polymorphic β-amyloid lesions present in individuals with Alzheimer's disease are collectively known as cerebral β-amyloidosis. Amyloid precursor protein (APP) transgenic mouse models similarly develop β-amyloid depositions that differ in morphology, binding of amyloid conformation-sensitive dyes, and Aβ40/Aβ42 peptide ratio. To determine the nature of such β-amyloid morphotypes, β-amyloid-containing brain extracts from either aged APP23 brains or aged APPPS1 brains were intracerebrally injected into the hippocampus of young APP23 or APPPS1 transgenic mice. APPPS1 brain extract injected into young APP23 mice induced β-amyloid deposition with the morphological, conformational, and Aβ40/Aβ42 ratio characteristics of β-amyloid deposits in aged APPPS1 mice, whereas APP23 brain extract injected into young APP23 mice induced β-amyloid deposits with the characteristics of β-amyloid deposits in aged APP23 mice. Injecting the two extracts into the APPPS1 host revealed a similar difference between the induced β-amyloid deposits, although less prominent, and the induced deposits were similar to the β-amyloid deposits found in aged APPPS1 hosts. These results indicate that the molecular composition and conformation of aggregated Aβ in APP transgenic mice can be maintained by seeded conversion.