Vascular Dysfunction Associated with Type 2 Diabetes and Alzheimer’s Disease: A Potential Etiological Linkage
Fuzhou Wang, Xirong Guo, Xiaofeng Shen, Richard M. Kream, Kirk J. Mantione, George B. Stefano
Department of Anesthesiology and Critical Care Medicine, Nanjing Maternit and Child Health Care Hospital, Nanjing Medical University, Nanjing, China (mainland)
Med Sci Monit Basic Res 2014; 20:118-129
Available online: 2014-08-01
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