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APOE Christchurch-mimetic therapeutic antibody reduces APOE-mediated toxicity and tau phosphorylation.

Claudia MarinoPaula Perez-CorredorMichael O'HareAnnie HeuerNatalia ChmielewskaHarper GordonAnita S ChandrahasLucia Gonzalez-BuendiaSantiago Delgado-TiradoTri H DoanTimothy E VanderleestSaid Arevalo-AlquichireRobert A ObarCarolina Ortiz-CorderoAndres VillegasDiego Sepulveda-FallaLeo A KimFrancisco LoperaRobert MahleyYadong HuangYakeel T QuirozJoseph F Arboleda-Velasquez
Published in: Alzheimer's & dementia : the journal of the Alzheimer's Association (2023)
We found that one of these antibodies, called 7C11, preferentially bound ApoE4, a major risk factor for sporadic AD, and disrupts heparin-ApoE4 interactions. We also determined the crystal structure of a Fab fragment of 7C11 and used computer modeling to predict how it would bind to ApoE. When we tested 7C11 in mouse models, we found that it reduced recombinant ApoE-induced tau pathology in the retina of MAPT*P301S mice and curbed pTau S396 phosphorylation in brains of systemically treated APOE4 knock-in mice. Targeting ApoE-HSPG interactions using 7C11 antibody may be a promising approach to developing new therapies for AD.
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