HYPERGLYCEMIC NEUROVASCULATURE-ON-A-CHIP TO STUDY THE AXIS OF DIABETES AND ALZHEIMER’S DISEASE

Diabetes mellitus (DM) is considered a risk factor for various type of dementia, which occurs due to brain damage [1].The prevalence of diabetes and neurodegenerative disease, including Alzheimer's disease (AD), is getting higher.In diabetic patients, hyperphosphorylation and aggregation of Tau proteins along with amyloid (A) plaques are observable, which is the most common pathological hallmarks of neurodegeneration.Based on the concept that AD may represent a brain-specific form of diabetes mellitus, the AD indicated "type-3 diabetes mellitus (T3DM)" [2].Accumulating evidence demonstrated that hyperglycemia/diabetes is a potential risk factor for neurodegenerative diseases, including AD. Hyperglycemia may increase blood-brain-barrier (BBB) permeability [3], allowing the influx of neurotoxic compounds into the brain.Disrupted endothelial integrity along with hyperglycemia might cause neurodegenerative disease, including vascular dementia and Alzheimer's disease.Diabetes/hyperglycemia-induced A production and plaque accumulation in the brain causing neurodegeneration.While the growing evidence represents diabetes as one of the risk factors for AD progression, however, it is unclear how hyperglycemia/diabetes can promote AD pathogenesis.Among the diverse molecular mechanisms by diabetes in neurodegenerative disease, SIRT1 (sirtuin 1, NAD+ dependent deacetylase) plays a role in BBB permeability [4], and has also been shown to ameliorate amyloidosis and tauopathy.However, how SIRT1 regulates hyperglycemia-induced endothelial injury and neurodegenerative process remains to be elucidated.