A lzheimer disease (AD) accounts for 60% to 80% of dementia cases and represents the most common cause of dementia among the elderly.1 AD is a chronic neurodegenerative disorder characterized by the development of cortical extracellular amyloid plaques, mainly consisting of amyloid β peptide (Aβ) and the intracellular neurofibrillary tangles formed by the aggregated tau protein.2 Aβ is a proteolytic cleavage product of amyloid precursor protein (APP), ubiquitously expressed in the body. APP is processed sequentially by γ-and β-secretases to generate a heterogeneous group of peptides among which Aβ42 and Aβ40 are believed to be particularly important in the pathogenesis of AD.3 Although Aβ remains in the focus of AD research, the pathogenesis of AD is largely undefined and effective treatments are still not available. 4 The interest in the role of vascular factors in pathogenesis of neurodegenerative dementias has grown steadily during the past decade. It is now well recognized that cerebrovascular dysfunction could be an essential factor in the pathogenesis of many types of dementia and significantly affects both incidence and course of the disease. 5Cerebrovascular impairment, including cerebral amyloid angiopathy, brain-blood barrier impairment, and small vessel disease, is frequently observed in patients with AD and could influence clinical manifestation and severity of AD and contribute to cognitive decline. 6 In addition, cardiovascular risk factors have been associated with higher risk of developing AD.7,8 Cardiovascular disease preventing strategies, like antihypertensive medications, were correlated with better mental health outcomes later in Abstract-Cerebrovascular impairment is frequent in patients with Alzheimer disease and is believed to influence clinical manifestation and severity of the disease. Cardiovascular risk factors, especially hypertension, have been associated with higher risk of developing Alzheimer disease. To investigate the mechanisms underlying the hypertension, Alzheimer disease cross talk, we established a mouse model of dual pathology by infusing hypertensive doses of angiotensin II into transgenic APPPS1 mice overexpressing mutated human amyloid precursor and presenilin 1 proteins. At 4.5 months, at the early stage of disease progression, only hypertensive APPPS1 mice presented impairment of temporal order memory performance in the episodic-like memory task. This cognitive deficit was associated with an increased number of cortical amyloid deposits (223±5 versus 207±5 plaques/mm 2 ; P<0.05) and a 2-fold increase in soluble amyloid levels in the brain and in plasma. Hypertensive APPPS1 mice presented several cerebrovascular alterations, including a 25% reduction in cerebral microvessel density and a 30% to 40% increase in cerebral vascular amyloid deposits, as well as a decrease in vascular endothelial growth factor A expression in the brain, compared with normotensive APPPS1 mice. Moreover, the brain levels of nitric oxide synthase 1 and 3 and the nitrite/nitrate levels were...