title: Common neurodegenerative pathways in obesity, diabetes, and Alzheimer's disease.
abstract: Cognitive decline in chronic diabetic patients is a less investigated topic. Diabetes and obesity are among the modifiable risk factors for Alzheimer's disease (AD), the most common form of dementia. Studies have identified several overlapping neurodegenerative mechanisms, including oxidative stress, mitochondrial dysfunction, and inflammation that are observed in these disorders. Advanced glycation end products generated by chronic hyperglycemia and their receptor RAGE provide critical links between diabetes and AD. Peripheral inflammation observed in obesity leads to insulin resistance and type 2 diabetes. Although the brain is an immune-privileged organ, cross-talks between peripheral and central inflammation have been reported. Damage to the blood brain barrier (BBB) as seen with aging can lead to infiltration of immune cells into the brain, leading to the exacerbation of central inflammation. Neuroinflammation, which has emerged as an important cause of cognitive dysfunction, could provide a central mechanism for aging-associated ailments. To further add to these injuries, adult neurogenesis that provides neuronal plasticity is also impaired in the diabetic brain. This review discusses these molecular mechanisms that link obesity, diabetes and AD. This article is part of a Special Issue entitled: Oxidative Stress and Mitochondrial Quality in Diabetes/Obesity and Critical Illness Spectrum of Diseases - edited by P. Hemachandra Reddy.
authors.affiliation: Section of Endocrinology, Veterans Affairs Medical Center, Denver, CO, USA; Department of Medicine, University of Colorado - Denver, Aurora, CO, USA. Electronic address: subbiah.pugazhenthi@ucdenver.edu.
authors.forename: Subbiah
authors.initials: S
authors.lastname: Pugazhenthi
authors.affiliation: Section of Endocrinology, Veterans Affairs Medical Center, Denver, CO, USA.
authors.forename: Limei
authors.initials: L
authors.lastname: Qin
authors.affiliation: Garrison Institute on Aging, Texas Tech University Health Sciences Center, Lubbock, TX, USA.
authors.forename: P Hemachandra
authors.initials: PH
authors.lastname: Reddy
mesh_terms: D000544:Alzheimer Disease / Q000209:etiology* / Q000378:metabolism* / Q000473:pathology; D000818:Animals; D001812:Blood-Brain Barrier / Q000378:metabolism / Q000473:pathology; D001921:Brain / Q000378:metabolism / Q000473:pathology; D048909:Diabetes Complications / Q000209:etiology* / Q000378:metabolism* / Q000473:pathology; D003920:Diabetes Mellitus / Q000378:metabolism* / Q000473:pathology; D017127:Glycation End Products, Advanced / Q000378:metabolism*; D006801:Humans; D007249:Inflammation / Q000150:complications / Q000378:metabolism / Q000473:pathology; D008928:Mitochondria / Q000378:metabolism / Q000473:pathology; D009765:Obesity / Q000150:complications* / Q000378:metabolism* / Q000473:pathology; D018384:Oxidative Stress; D000067759:Receptor for Advanced Glycation End Products / Q000378:metabolism
chemical_list: D017127:Glycation End Products, Advanced; D000067759:Receptor for Advanced Glycation End Products
keywords: Advanced glycation end products; Alzheimer's disease; Diabetes; Inflammation; Mitochondria; Obesity; Oxidative stress