Advanced glycation end products, dementia, and diabetes

摘要: It is becoming abundantly clear that the insight into pathological process of Alzheimer’s disease (AD) provided through autosomal dominant variants condition only a partial one. The formation and aggregation Aβ phosphorylation tau are clearly part core pathogenesis. However, although these may be necessary processes, indeed in familial forms possibly also sufficient they not whole story common late-onset disease. Here, mixed pathologies norm at post mortem plaques tangles formed by accompanied inflammation vascular This finding congruent with epidemiology has long pointed to three substantial factors alter risk dementia other than age: head injury, anti-inflammatory drugs, diabetes. reasonably why injury drugs might affect but relationship between diabetes been far less clear. could simply increases related damage brain as it does limbs, kidneys, organs. More interesting molecular scientists observations insulin signaling modifies amyloid precursor protein (APP) metabolism cells animal models, suggesting possible influence metabolic pathways on canonical pathway AD. Most intriguing all observation such processes AD, aging or longevity itself. In PNAS, Cai et al. (1) shed light complex interactions point clinical implications, including both biomarkers potential therapeutics. line considerable evidence for an oxidant-mediated pathogenic effect, show pro-oxidant diet mice induces β-cleaved APP generation. At same time mice, fed methyl-glyoxyl (MG) derivatives, had increased weight systemic resistance. human cohort, dietary MG levels accompanying advanced glycation end products (AGEs) correlated positively cognitive deficits decline inversely survival factor sirtuin-1 (SIRT1) markers sensitivity.