APP and Alzheimer disease: PdgfrβF7/F7 mice, which have disrupted PDGFRβ signalling, have a more pronounced vascular phenotype associated with vascular loss and BBB leakiness [11], and when Pdgdfβ+/− heterozygous mice were crossed with Tg-APP mice, there was accelerated Aβ accumulation and clinical disease progression [8], supporting recent studies indicating that vascular dysfunction is one of the earliest pathological features in pre-clinical AD [12].