It has been suggested that the vulnerability of the aged brain to Alzheimer's disease (AD) pathogenesis depends on a number of risk factors, including abnormal glycolytic metabolism and β-amyloid accumulation. Intrahippocampal injections of β-amyloid and related peptides were administered to chronically hyperglycemic rats to examine β-amyloid toxicity and the interaction with imbalances of glucose metabolism. Chronic hyperglycemia was induced by systemic injection of streptozotocin (STZ) which selectively destroys pancreatic β-islet cells. Ten days after intrahippocampal injection of synthetic β-amyloid peptides (β1-42, β25-35, scrambled β25-35), lesion volume, blood glucose, and plasma corticosterone concentrations, β1-42 immunoreactivity and gliosis were assessed to determine peptide toxicity in the normoglycemic and hyperglycemic conditions. Glucose levels correlated with plasma corticosterone concentrations (r = 0.85) and increased lesion volume size (r = 0.36). Intrahippocampal peptide injections in normoglycemic subjects did not induce significant damage as compared to control injections of vehicle alone. STZ-treated groups demonstrated a trend for increased lesion volume size following injection of either vehicle, β1-42, or β25-35. The combination of the β1-42 peptide and streptozotocin-induced hyperglycemia was toxic and induced significantly larger lesions (p < 0.01) of the dorsal blade of the dentate gyrus as compared to injections of β1-42 into normoglycemic subjects.
- Alzheimer's disease