Compounds termed advanced glycation endproducts (AGEs), present in the Western diet and previously linked to diabetes and to neurodegenerative disease, may be one possible cause of the accumulation of amyloid, a component of the plaques characteristic of Alzheimer’s disease. AGEs have been linked to dementia when present in the bloodstream and the brain at high levels, but the mechanism behind the link is largely unknown. Helen Vlassara and colleagues tracked cognitive health in mice that ingested certain harmful AGEs at levels proportional to a Western diet to determine whether AGEs cause neurodegeneration by suppression of SIRT1, a deacetylase enzyme with protective neuronal, immune, and endocrine functions. SIRT1 is abnormally low in individuals with brain and metabolic diseases, including aging and diabetes. The authors report that mice fed the high-AGE diet had high levels of AGEs in their brains, and low levels of SIRT1 in their blood and brain tissue, compared with mice fed a diet low in AGEs. Mice fed a high-AGE diet also developed cognitive and motor dysfunction, amyloid-β deposits, and insulin resistance, a pre-diabetic condition. Mice fed half the amount of AGEs did not display these changes. In addition, in a clinical study of healthy humans over the age of 60, individuals who had high AGEs in their blood also had low SIRT1 levels in their blood and developed cognitive decline over a nine month period as well as insulin resistance. According to the authors, dietary AGEs might contribute to dementia, possibly by suppressing SIRT1.
