Early buildup of brain plaques prevents small blood vessel amyloid in genetically modified mice

Tg-SwDI/Tg-5xFAD mice exhibited larger parenchymal amyloid plaques compared to Tg-5xFAD mice.

• Bigenic mice showed elevated accumulation of Aβ and fibrillar amyloid in the brain compared to single transgenic lines.
• Microvascular amyloid, typical of Tg-SwDI mice, was absent in the bigenic Tg-SwDI/Tg-5xFAD mice.
• The larger parenchymal amyloid plaques in bigenic mice were correlated with a greater loss of cortical neurons and increased activated microglia.
• The edges of parenchymal amyloid plaques were largely made up of CAA mutant Aβ.
• Non-mutated Aβ fibril seeds may facilitate the formation of CAA mutant Aβ fibrils in laboratory settings.
• Injected CAA mutant Aβ peptide accumulated on and around existing parenchymal amyloid plaques in Tg-5xFAD mice.

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