Detection of vascular alterations by in vivo magnetic resonance angiography and histology in APP/PS1 mouse model of Alzheimer's disease

Abstract : Object: The brain of patients with Alzheimer’s disease (AD) is characterized by the presence of amyloid plaques and neurofibrillary tangles. Vascular alterations such as amyloid angiopathy are also commonly reported in patients with AD and participate in mechanisms involved in disease onset and progression. Transgenic mouse models of AD have been engineered to evaluate the pathophysiology and new treatments of the disease. Our study evaluated vascular alterations in APP$_{SweLon}$/PS1$_{M146L}$ mouse model of AD. Materials and methods: Histological analysis and in vivo magnetic resonance angiography protocols based on time of flight (TOF) and contrast-enhanced (CE) angiography were applied to evaluate cerebrovascular alterations. Results Histological analysis showed that cerebrovascular amyloid deposition starts by the same time as extracellular amyloid plaques. However, unlike plaques deposition, severity of cerebrovascular alterations is stabilized in older animals. Alteration of the middle cerebral artery was detected in old APP$_{SweLon}$/PS1$_{M146L}$ mice with respect to adult ones by evaluating the severity of vessel voids and the reduction of vessel length on TOF- and CE-angiograms. Agerelated alterations in control PS1 mice were only detected as a reduced vessel length on CE-angiograms. Conclusion These results show that macroscopic vascular abnormalities are part of the pathological alterations developed by APP$_{SweLon}$/PS1$_{M146L}$ mouse models of AD.