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(American Journal of Pathology. 2005;167:527-543.)
© 2005 American Society for Investigative Pathology

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

Samir Kumar-Singh^*, Daniel Pirici^*, Eileen McGowan, Sally Serneels^*, Chantal Ceuterick, John Hardy, Karen Duff^¶, Dennis Dickson and Christine Van Broeckhoven^*

From the Department of Molecular Genetics,^* Flanders Interuniversity Institute for Biotechnology (VIB8), and the Laboratory of Electron Microscopy, Institute Born Bunge and University of Antwerp, Antwerp, Belgium; the Departments of Neuroscience and Pathology, Mayo Clinic, Jacksonville, Florida; the Laboratory of Neurogenetics, National Institute on Aging/National Institutes of Health, Bethesda, Maryland; and the Center for Dementia Research,^¶ Nathan S. Kline Institute, Orangeburg, New York

Occurrence of amyloid ß (Aß) 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 Aß 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 Aß, our data suggest that perturbed vascular transport and/or perivascular enrichment of Aß leads to the formation of vasocentric dense plaques in Tg2576 and PSAPP mouse models of AD.

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