Investigating Alzheimer’s Disease‐Related Pathology in a Chronic Hyperglycemic Mouse Model

Abstract

AbstractBackgroundDiabetes is a major risk factor for Alzheimer’s disease (AD). Hyperglycemia is the primary characteristic of diabetes. Hyperglycemia was induced in both young and aged mice. Following an incubation period, a hyperglycemic rescue was introduced to lower hyperglycemia, and to determine if hyperglycemia itself, or neuroinflammation as a result of hyperglycemia, increased AD pathology (i.e., hyperphosphorylated tau and reactive gliosis).MethodYoung (7‐month‐old; N = 24) and aged (18 month old; N = 24) C57BL/6J (wildtype) mice were injected with a low and staggered dose of streptozotocin (STZ) to induce sustained hyperglycemia. After a 9‐week incubation period of hyperglycemia (e.g., +250mg/dl), a group of mice were treated with Phloridzin (PZ) ‐ a drug that reduces hyperglycemia by preventing renal and intestine glucose uptake ‐ for two consecutive weeks to determine if hyperglycemia itself or the subsequent neuroinflammation, is what increase the risk for AD.ResultSTZ increased hyperglycemia levels; PZ lowered hyperglycemia levels. Both young and aged STZ, PZ, and STZ+PZ mice showed significantly differences in P‐S396‐tau/total, P‐T181‐tau/total, proinflammatory cytokines, and increases reactive microglia and astrocytes compared to controls.ConclusionPZ did not rescue hyperglycemic‐induced AD pathology.