Early-onset Formation of Parenchymal Plaque Amyloid Abrogates Cerebral Microvascular Amyloid Accumulation in Transgenic Mice

May 16, 2014The Journal of biological chemistry

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

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Abstract

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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