Vascular dysfunction—The disregarded partner of Alzheimer's disease

Abstract

Increasing evidence recognizes Alzheimer's disease (AD) as a multifactorial and heterogeneous disease with multiple contributors to its pathophysiology, including vascular dysfunction. The recently updated AD Research Framework put forth by the National Institute on Aging-Alzheimer's Association describes a biomarker-based pathologic definition of AD focused on amyloid, tau, and neuronal injury. In response to this article, here we first discussed evidence that vascular dysfunction is an important early event in AD pathophysiology. Next, we examined various imaging sequences that could be easily implemented to evaluate different types of vascular dysfunction associated

Metabolic compartmentalization between astroglia and neurons in physiological and pathophysiological conditions of the neurovascular unit

“…[21][22][23] Now, the NVU is a tool that can be used to understand normal brain physiology as well as the pathophysiology of numerous neurological disorders. [24][25][26][27][28][29] Conversely, the malfunction of astroglia in the NVU (i.e., "astrogliopathy") [30][31][32][33][34] induces neuronal dysfunction, leading to various neurological disorders including cerebrovascular disease (e.g., stroke and small vessel disease-like Binswanger's disease and cerebral autosomaldominant arteriopathy with subcortical infarct and leukoencephalopathy [CADASIL]/ 35 cerebral autosomal recessive arteriopathy with subcortical infarct and leukoencephalopathy [CARASIL]), 36,37 neurodegenerative disease (e.g., Alzheimer's disease, 38,39 Parkinson's disease, 40,41 and amyotrophic lateral sclerosis [ALS]), [42][43][44] and neuroimmunological disease (e.g., multiple sclerosis [MS], [45][46][47][48] and neuromyelitis optica spectrum disorder [NMOSD]). 49,50 This review will focus on the supportive roles of astroglia in the NVU from the perspective of three major metabolic compartments with neurons: (i) glucose and lactate; (ii) fatty acid and ketone bodies (KBs); and (iii) D-and L-serine.…”

Plasma biomarkers of astrocytic and neuronal dysfunction in early‐ and late‐onset Alzheimer's disease

“…Importantly, genetics of AD support a critical role for glia and neuroinflammation in AD, whereas clinical studies suggest prevalent presence of pathologies affecting the brain's white matter . Overall, vascular health, gliopathy, and neuroinflammation appear to contribute to disease progression . Consequently, a better characterization of primary immuno‐vascular dysregulations and the related changes in synaptic plasticity in AD emerge as critical areas of research.…”

Cerebral atherosclerosis contributes to Alzheimer’s dementia independently of its hallmark amyloid and tau pathologies

“…Both b-amyloid and neurofibrillary tangle pathologies have been studied extensively and found to contribute to synaptic loss, mitochondrial dysfunction, alterations in neuronal activity, and neurodegeneration [1][2][3] . Yet, it is increasingly recognized that multiple pathologies contribute to the clinical diagnosis of AD dementia in addition to its hallmark pathologies [4][5][6][7][8] . Notably, cerebral atherosclerosis is an important contributor to the development of AD dementia [8][9][10][11] and associated with approximately three times higher risk for AD dementia and nine times higher risk for vascular dementia [12][13][14][15] .…”