2016 Volume 62 Issue Suppl.1 Pages 75
Purpose: Alzheimer disease (AD), involved the abnormal metabolism of β-amyloid and tau, is the major cause of dementia among elderly. Diabetes mellitus (DM) has been identified as a risk factor of AD. Two pathological lesions of AD, Aβ plaques and neurofibrillary tangles, are linked to neuroinflammation and lipid peroxidation, are also induced by abnormal glucose metabolism. Here, we examined the effects of experimental DM in tau transgenic mice Tg601 (overexpressing wild-type human tau) and analyzed the brain regional difference occurred due to DM in AD.
Methods: Hippocampus, midbrain and cerebellum were analyzed from streptozotocin (STZ) injected of Tg601 and non-transgenic (NTg) mice. Immunoblotting and immunohistochemistry (IHC) were performed to assess tau hyperphosphorylation, and IHC to evaluate Ionized calcium binding adaptor molecule-1 (Iba-1) and CD68 positive microglia. Inflammatory cytokines including IL-1β, IL-6, and IL-10 were assayed using multiplexed bead based immunoassay. IL-18 was measured by enzyme linked immunosorbent assay (ELISA) and lipid peroxidation products 4-hydroxy-trans-2-noneal (HNE) and malondialdehyde (MDA) by ELISA and thiobarbituric acid reactive substances assay, respectively.
Results: STZ injection induced tau hyperphosphorylation, as detected by AT8 and AT180 antibodies, in the hippocampus, but not in the cerebellum or midbrain of Tg601 and NTg mice. STZ treatment also elevated the number of Iba1-positive microglial cells, levels of IL-1β, IL-6, IL-10 and IL-18, and lipid peroxidation markers MDA or HNE in the hippocampus of the brain.
Conclusions: These results indicated that hyperglycemia-induced tau hyperphosphorylation, neuroinflammation and oxidative stress occurred more severely in the hippocampus than other parts of the brain and could contribute to selective neurodegeneration in human AD.
