Thomas S, Hoxha K, Tran A, Prendergast GC

Alzheimer's disease (AD) is an irreversible, progressive brain disorder responsible for memory loss leading to the inability to carry out the simplest tasks. AD is one of the leading causes of death in the United States. As yet there are no effective medications to treat this debilitating disease. In recent ...

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years, a human gene called bridging integrator 1 (BIN1) has emerged as one of the most important genes in affecting the incidence of sporadic AD. Bin1 can directly bind to Tau and mediates late onset AD risk by modulating Tau pathology. Recently our group found Bin1 antibody could exert drug-like properties in an animal model of ulcerative colitis. We hypothesized that the Bin1 monoclonal antibody (mAb) could be used in the treatment of AD by lowering the levels of Tau in cell culture and animal models. Cell culture studies confirmed that the Bin1 mAb (99D) could lower the levels of phosphorylated Tau (pTau). Multiple mechanisms aided by endosomal proteins and Fc gamma receptors are involved in the uptake of Bin1 mAb into cells. In Tau expressing cell culture, the Bin1 mAb induces the proteasome machinery leading to ubiquitination of molecules thereby preventing cell stress. In vivo studies demonstrated that treatment of P301S mice expressing Tau with the Bin1 mAb survived longer than the untreated mice. Our data confirm that Bin1 mAb lowers the levels of pTau and could be a drug candidate in the treatment of AD.

Date: Oct. 01, 2019

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