Dense-Core Plaques in Tg2576 and PSAPP Mouse Models of Alzheimer’s Disease Are Centered on Vessel Walls

摘要

Occurrence of amyloid β (Aβ) dense-core plaques in the brain is one of the chief hallmarks of Alzheimer’s disease (AD). It is not yet clear what factors are responsible for the aggregation of Aβ in the formation of these plaques. Using Tg2576 and PSAPP mouse models that exhibit age-related development of amyloid plaques similar to that observed in AD, we showed that ≈95% of dense plaques in Tg2576 and ≈85% in PSAPP mice are centered on vessel walls or in the immediate perivascular regions. Stereoscopy and simulation studies focusing on smaller plaques suggested that vascular associations for both Tg2576 and PSAPP mice were dramatically higher than those encountered by chance alone. We further identified ultrastructural microvascular abnormalities occurring in association with dense plaques. Although occurrence of gross cerebral hemorrhage was infrequent, we identified considerable infiltration of the serum proteins immunoglobulin and albumin in association with dense plaques. Together with earlier evidence of vascular clearance of Aβ, our data suggest that perturbed vascular transport and/or perivascular enrichment of Aβ leads to the formation of vasocentric dense plaques in Tg2576 and PSAPP mouse models of AD.