Advanced glycation endproducts as gerontotoxins and biomarkers for carbonyl-based degenerative processes in Alzheimer's disease

Abstract

Alzheimer's disease (AD) is the most common dementia disorder of later life. Although there might be various different triggering events in the early stages of the disease, they appear to converge on a few characteristic final pathways in the late stages, characterized by inflammation and neurodegeneration. Here, we review the hypothesis that advanced glycation end products (AGEs), which reflect carbonyl stress, an imbalance between the production of reactive carbonyl compounds and their detoxification, can serve as biomarkers for the progression of disorder. AGE modification may explain many of the neuropathological and biochemical features of AD, such as extensive protein cross-linking shown as amyloid plaques and neurofibrillary tangles, inflammation, oxidative stress and neuronal cell death. Although accumulation of AGEs is a normal feature of aging, it appears to be significantly accelerated in AD. We suggest that higher AGE concentrations in brain tissue and in cerebrospinal fluid might be able to distinguish between normal aging and AD.

Overlapped Metabolic and Therapeutic Links between Alzheimer and Diabetes

“…AGEs particularly produce superoxides and hydrogen peroxides, and their production is associated with related proteins and sugars oxidative insult. Furthermore, AGEs also produce ROS by the metalcatalysed Fenton reaction that result in site-specific attack on proteins and lipid peroxidation [173,[258][259][260].…”

Association between advanced glycation end-products and functional performance in Alzheimer's disease and mixed dementia

“….................................................................................................................................................................................................................................................................................................................................................................................................................................................... In accordance with the results of this study, it would be interesting to investigate whether decline in functional mobility can be attenuated by reducing AGEs levels. Excessive elevation of glucose concentration, such as in DM, most likely accelerates the glycation of proteins (Ahmed and Thornalley, 2007;Rahmadi et al, 2011). Intensive glycaemic control may be a method to decrease AGEs formation.…”

Advanced glycation end products and neurodegenerative diseases: Mechanisms and perspective

“…Large scale and long term retrospective studies are required to evaluate the potential of AGEs as reliable biomarkers of neurodegenerative diseases, although it is proposed that higher AGE concentrations in brain tissue and in cerebrospinal fluid are able to distinguish between normal aging and AD [50]. Once confirmed, we could utilize AGEs for the early diagnosis of neurodegenerative diseases.…”