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From the Department of Medicine,* Health Sciences Center, Stony Brook University, Stony Brook, New York; and the Departments of Pathology and Neurology, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands
Cerebral vascular amyloid ß-protein (Aß) deposition, also known as cerebral amyloid angiopathy, is a common pathological feature of Alzheimer’s disease. Additionally, several familial forms of cerebral amyloid angiopathy exist including the Dutch (E22Q) and Iowa (D23N) mutations of Aß. Increasing evidence has associated cerebral microvascular amyloid deposition with neuroinflammation and dementia in these disorders. We recently established a transgenic mouse model (Tg-SwDI) that expresses human vasculotropic Dutch/Iowa mutant amyloid ß-protein precursor in brain. Tg-SwDI mice were shown to develop early-onset deposition of Aß exhibiting high association with cerebral microvessels. Here we present quantitative temporal analysis showing robust and progressive accumulation of cerebral microvascular fibrillar Aß accompanied by decreased cerebral vascular densities, the presence of apoptotic cerebral vascular cells, and cerebral vascular cell loss in Tg-SwDI mice. Abundant neuroinflammatory reactive astrocytes and activated microglia strongly associated with the cerebral microvascular fibrillar Aß deposits. In addition, Tg-SwDI mouse brain exhibited elevated levels of the inflammatory cytokines interleukin-1ß and -6. Together, these studies identify the Tg-SwDI mouse as a unique model to investigate selective accumulation of cerebral microvascular amyloid and the associated neuroinflammation.
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