01 August 2014 : Review article
Vascular Dysfunction Associated with Type 2 Diabetes and Alzheimer’s Disease: A Potential Etiological LinkageFuzhou WangABDEFG, Xirong GuoBDEFG, Xiaofeng ShenBDEF, Richard M. KreamDEFG, Kirk J. MantioneDEFG, George B. StefanoABDEFG
Med Sci Monit Basic Res 2014; 20:118-129
The endothelium performs a crucial role in maintaining vascular integrity leading to whole organ metabolic homeostasis. Endothelial dysfunction represents a key etiological factor leading to moderate to severe vasculopathies observed in both Type 2 diabetic and Alzheimer’s Disease (AD) patients. Accordingly, evidence-based epidemiological factors support a compelling hypothesis stating that metabolic rundown encountered in Type 2 diabetes engenders severe cerebral vascular insufficiencies that are causally linked to long term neural degenerative processes in AD. Of mechanistic importance, Type 2 diabetes engenders an immunologically mediated chronic pro-inflammatory state involving interactive deleterious effects of leukocyte-derived cytokines and endothelial-derived chemotactic agents leading to vascular and whole organ dysfunction. The long term negative consequences of vascular pro-inflammatory processes on the integrity of CNS basal forebrain neuronal populations mediating complex cognitive functions establish a striking temporal comorbidity of AD with Type 2 diabetes. Extensive biomedical evidence supports the pivotal multi-functional role of constitutive nitric oxide (NO) production and release as a critical vasodilatory, anti-inflammatory, and anti-oxidant, mechanism within the vascular endothelium. Within this context, we currently review the functional contributions of dysregulated endothelial NO expression to the etiology and persistence of Type 2 diabetes-related and co morbid AD-related vasculopathies. Additionally, we provide up-to-date perspectives on critical areas of AD research with special reference to common NO-related etiological factors linking Type 2 diabetes to the pathogenesis of AD.
Keywords: Endothelium, Vascular - physiopathology, Diabetes Mellitus, Type 2 - physiopathology, Alzheimer Disease - physiopathology, Vascular Diseases - physiopathology
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