Abstract
Given the unprecedented rise in the world’s population, the prevalence of prominent age-related disorders, like cardiovascular disease and dementia, will further increase. Recent experimental and epidemiological evidence suggests a mechanistic overlap between cardiovascular disease and dementia with a specific focus on the linkage between arterial stiffness, a strong independent predictor of cardiovascular disease, and/or hypertension with Alzheimer’s disease. In the present study, we investigated whether pharmacological induction of arterial stiffness and hypertension with angiotensin II (1 µg·kg−1·min−1 for 28 days via an osmotic minipump) impairs the progression of Alzheimer’s disease in two mouse models (hAPP23+/− and hAPPswe/PSEN1dE9 mice). Our results show increased arterial stiffness in vivo and hypertension in addition to cardiac hypertrophy after angiotensin II treatment. However, visuospatial learning and memory and pathological cerebral amyloid load in both Alzheimer’s disease mouse models were not further impaired. It is likely that the 28-day treatment period with angiotensin II was too short to observe additional effects on cognition and cerebral pathology.
Highlights
The average age of the world’s population is steadily increasing
From a translational point of view, we study the exposure to angiotensin II (AngII) in adult rodents (6 months of age) to mimic early-onset hypertension, since early-onset rather than late-onset hypertension appears to be related to mild cognitive impairment [35]
We aimed to investigate the mechanistic convergence between pharmacologically induced arterial stiffness (AS) and Alzheimer’s disease (AD) in two well-validated murine models of AD, i.e., hAPP23+/− and hAPPswe/PSEN1dE9, on a C57BL/6 background
Summary
The number of people aged 65 and older is estimated to reach 1.4 billion in 2030 and 2.1 billion in 2050, up from 1 billion in 2020 [1] This unprecedented rise in the world’s elderly population will increase the prevalence of age-related disorders, such as cardiovascular disease (CVD) and dementia. Previous research demonstrated that blood pressure elevation appears decades before the onset of AD, followed by a gradual reduction in blood pressure years before the onset of AD [23,24] This phenomenon makes studying the link between hypertension and AD challenging and less accurate. In contrast to blood pressure measurements, PWV increases [33] in a sustained manner over several decades prior to the diagnosis of dementia [34], suggesting that AS is a driving factor linking hypertension, cognitive impairment and consequent neuroanatomical changes. After approximately 14 days, the experimental test battery started with Morris water ris water maze (MWM)
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