Exogenous induction of cerebral β-amyloidosis in βAPP-transgenic mice

The expanding realm of prion phenomena in neurodegenerative disease

“…27 Induction of Aβ pathology from an exogenous seed has also been described in mice expressing APP, the holoprotein from which Aβ is cleaved. In these mice, Aβ deposition and Aβ angiopathy develop with age or can be induced prematurely by injecting cortical extracts from either AD patients 28 or aged βAPP mice. 29 Injecting these extracts into wild-type mice has no effect and Aβ-immunodepleted extracts fail to induce pathology.…”

Alzheimer disease

“…The strongest in vivo evidence comes from a large body of work demonstrating that injection of misfolded Aβ from either biological or synthetic sources at specific loci in the brains of AD model mice accelerates the appearance of aggregated, transgenically expressed Aβ throughout the brain. 42,[59][60][61][62] While these seed-induced Aβ deposits are initially observed in tissue directly surrounding sites of seeding, spreading eventually occurs along axonally connected regions and in separate locations, suggesting that both axonal transport and extracellular routes play a role in the spreading of Aβ throughout the brain.…”

Alzheimer's Disease and Prion Protein

“…Thus, a prionbased mechanism is proposed to unite a wide array of neurodegenerative diseases, all of which may stem from misfolded proteins self-propagating through the brain (103,108). Local injection of misfolded Aβ in the brains of AD transgenic mice has been found to trigger the misfolding and spreading of otherwise normal Aβ throughout the brain, indicating the prion-like activity of Aβ (108)(109)(110)(111)(112)(113)(114). Injection of AD brain extracts into the hippocampus of mice expressing human wild-type APP induces Aβ deposition, which progressively increases over time after inoculation and spreads to brain areas far from the injection site, where other Aβ-related pathology is also observed (114).…”