Alzheimer’s disease (AD) is one of the most common causes of severe cognitive impairment among the elderly (Ott et al. 1995). AD is a progressive neurodegenerative disorder, primarily characterized by neuronal loss, formation of intraneuronal neurofibrillary tangles (NFTs) and accumulation of β-amyloid peptides (Aβ), as plaques in brain parenchyma or as cerebral amyloid angiopathy (CAA) in blood vessels (Reitz and Mayeux 2014). Additionally, structural brain abnormalities, blood-brain-barrier (BBB) dysfunction, brain atrophy, and neuroinflammation have been associated with AD pathology, correlated with a gradual decline in cognition (Querfurth and LaFerla 2010). To date, the exact mechanisms underlying AD pathogenesis remain unclear, as are
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Indeed, many studies have demonstrated that vascular pathology plays a central role in AD pathogenesis. Accordingly, CVD and several cardiovascular risk factors (e.g. atherosclerosis, heart failure, hypertension, hyperhomocysteinemia, and diabetes mellitus) or their potential consequences (chronic cerebral hypoperfusion, hypoxia, and ischemia) have been associated with the development of AD (Hachinski and Munoz 1997; la Torre 2004; Pimentel-Coelho and Rivest 2012; la Torre 2012; Kelleher and Soiza 2013; Zhao and Gong 2015). Other evidence supporting the notion that AD can be considered a cerebrovascular disorder is suggested to lie in the fact that AD and vascular dementia (VaD), an acknowledged vascular disorder, share almost all the same clinical symptoms and risk factors, and are thought to benefit from the same therapies (Alvarez et al., 2008). However, the exact pathophysiological pathways underlying the interaction between vascular dysfunction, flow disturbances, AD-related pathology and cognitive decline are poorly understood. There is ample and convincing evidence that vascular oxidative stress can cause profound deficits in neurovascular regulation associated with many diseases, but likely also in non-pathological aging (Hui Liu and Zhang 2012). Moreover, many cardiovascular risk factors have been reported to lead to mitochondrial dysfunction
Indeed, many studies have demonstrated that vascular pathology plays a central role in AD pathogenesis. Accordingly, CVD and several cardiovascular risk factors (e.g. atherosclerosis, heart failure, hypertension, hyperhomocysteinemia, and diabetes mellitus) or their potential consequences (chronic cerebral hypoperfusion, hypoxia, and ischemia) have been associated with the development of AD (Hachinski and Munoz 1997; la Torre 2004; Pimentel-Coelho and Rivest 2012; la Torre 2012; Kelleher and Soiza 2013; Zhao and Gong 2015). Other evidence supporting the notion that AD can be considered a cerebrovascular disorder is suggested to lie in the fact that AD and vascular dementia (VaD), an acknowledged vascular disorder, share almost all the same clinical symptoms and risk factors, and are thought to benefit from the same therapies (Alvarez et al., 2008). However, the exact pathophysiological pathways underlying the interaction between vascular dysfunction, flow disturbances, AD-related pathology and cognitive decline are poorly understood. There is ample and convincing evidence that vascular oxidative stress can cause profound deficits in neurovascular regulation associated with many diseases, but likely also in non-pathological aging (Hui Liu and Zhang 2012). Moreover, many cardiovascular risk factors have been reported to lead to mitochondrial dysfunction