Role of stereotaxically injected IgG from db/db mice in the phosphorylation of the microtubule-associated protein tau in hippocampus

Abstract

People with type 2 diabetes (T2DM) mellitus are high risk for dementia and Alzheimer's disease (AD) via several plausible pathways. However, the underlying mechanisms have been still unclear, and the relation of immune injury to the pathogenesis of T2DM-related AD is not yet completely understood. Our present study aimed to elucidate the possible role of immunoglobulin IgG in the immune process of AD associated with T2DM in db/db mice. Hippocampi of 20 db/db mice and 20 C57BL/6 mice were subjected to immunohistochemistry and immunofluorescence assays. The phosphorylation of tau, glycogen synthase kinase (GSK)-3β and AKT activity was examined by Western blot analysis. IgG purified from the sera of IgG deposit-positive db/db mice was stereotaxically injected into the hippocampi of another 12 db/db mice and 12 C57BL/6 mice. The phosphorylation of tau, Abeta, GSK-3β and AKT activity was analyzed. Compared with the C57BL/6 control, 13 of the 20 db/db mice exhibited high levels of IgG deposits in the hippocampus. Treatment with IgG triggered tau hyperphosphorylations and Abeta deposition, which are likely major factors in AD. Meanwhile, IgG inhibited AKT phosphorylation and promoted GSK-3β activity. The IgG deposits observed in some db/db mice were possibly related to the impairment of T2DM-related AD development. Some autoimmune processes may be involved in AD in type 2 diabetes mellitus development at the level of the hippocampus.