Inflammation, Nitro-Oxidative Stress, Impaired Autophagy, and Insulin Resistance as a Mechanistic Convergence Between Arterial Stiffness and Alzheimer’s Disease

Abstract

The average age of the world’s elderly population is steadily increasing. This unprecedented rise in the aged world population will increase the prevalence of age-related disorders such as cardiovascular disease (CVD) and neurodegeneration. In recent years, there has been an increased interest in the potential interplay between CVDs and neurodegenerative syndromes, as several vascular risk factors have been associated with Alzheimer’s disease (AD). Along these lines, arterial stiffness is an independent risk factor for both CVD and AD. In this review, we discuss several inflammaging-related disease mechanisms including acute tissue-specific inflammation, nitro-oxidative stress, impaired autophagy, and insulin resistance which may contribute to the proposed synergism between arterial stiffness and AD.

The KEAP1-NRF2 System in Healthy Aging and Longevity

“…Low levels of endogenous antioxidants and increased reactive species have also been described in PD [ 121 ]. In addition to reduced antioxidant capacities, a number of reports have described the so-called neuroinflammatory status in AD and PD models and patients [ 122 , 123 , 124 , 125 ].…”

Long-Term Pharmacological Inhibition of the Activity of All NOS Isoforms Rather Than Genetic Knock-Out of Endothelial NOS Leads to Impaired Spatial Learning and Memory in C57BL/6 Mice

“…However, epidemiological studies increasingly report an independent, mechanistic convergence between both pathological syndromes. In recent decades, there has been increasing interest in the role of arterial stiffness in neurodegeneration, as it was found to be an independent risk factor for both CVD and neurodegeneration [ 1 , 2 , 3 , 4 ]. Although overwhelming evidence demonstrates an association between arterial stiffness and neurodegeneration in human subjects, these studies are limited by correlative evidence.…”

“…Although nitric oxide (NO) is a small gaseous signaling molecule, it has a well-defined importance in not only arterial stiffness [ 4 , 5 , 6 ], but also in neurodegeneration [ 7 , 8 , 9 , 10 ]. Studies in murine models of NO dysfunction through the inhibition of nitric oxide synthase (NOS) with N(G)-nitro-L-arginine methyl ester (L-NAME) or by a genetic knockout of endothelial NOS (eNOS −/− ) [ 11 , 12 ], have shown the importance of NO in arterial stiffness.…”

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

“…Dementia, on the other hand, was the seventh leading cause of death in 2019 with an estimated death toll of 1.6 million people, with Alzheimer’s disease (AD) being the most prominent dementia syndrome [ 3 ] presenting a broad range of symptoms from motor dysfunctions to psychobehavioral manifestations [ 4 ]. The most common early manifestations of AD are loss of short-term memory, visuospatial dysfunction, impaired reasoning and language dysfunction, with cerebral β-amyloid accumulation and neurofibrillary tangles as the two major neuropathological hallmarks of the disease [ 5 , 6 ].…”

“…There is evidence that increased pulse wave velocity (PWV), an in vivo marker of AS, is associated with more rapid cognitive decline [ 6 , 28 ] and neuroanatomical changes associated with AD [ 29 , 30 , 31 ]. Hughes et al, showed that AS, as measured by PWV, is associated with the amount of cerebral Aβ deposition and that AS is an independent predictor of progressive Aβ deposition [ 32 ].…”