Transgenic mice expressing the vasculotropic Dutch/Iowa (E693Q/D694N) mutant human Aβ precursor protein in brain (Tg-SwDI) accumulate abundant cerebral microvascular fibrillar amyloid deposits and exhibit robust neuroinflammation. In vitro, the doubly mutated Aβ peptides showed an increased propensity to fibrillation and pathogenicity compared to the Dutch and Iowa single mutants.