Short-Term Pharmacological Induction of Arterial Stiffness and Hypertension with Angiotensin II Does Not Affect Learning and Memory and Cerebral Amyloid Load in Two Murine Models of Alzheimer’s Disease

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 (1µg·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.

Aging of the Arterial System

“…Indeed, increased arterial stiffness causes an excessive pulsatile energy in the brain microvascular bed due to insufficient flow wave damping, thus promoting the onset of microbleeds [ 85 ]. Studies on murine models also showed that the short-term pharmacological induction of arterial stiffness does not cause additional effects on mouse models of Alzheimer, suggesting a pathogenetic role of long-lasting arterial stiffness [ 86 ]. Recent studies also reported a positive association between local amyloid-β and regional tau burden and aortic stiffness [ 84 ], but its exact cause–effect relation deserves further studies.…”