Loss of deep cerebellar nuclei neurons in the 3xTg-AD mouse and protection by an anti-Aβ antibody fragment

Running title: 3xTg-AD mouse cerebellum protected by scFv-h3D6 1 These authors made equally important contributions to this study. A u t h o r ' s d r a f t v e r s i o n Draft version of: Esquerda-Canals, Gisela, et al. " Loss of deep cerebellar nuclei neurons in the 3xTg-AD mice and protection by an anti-amyloid β antibody fragment " in MAbs (ed. Abstract The therapeutic potential of scFv-h3D6 has recently been shown in the 3xTg-AD mouse. A clear effect on Aβ-oligomers and certain apolipoproteins in the brain was found, but no effect was seen in the cerebellum. Here, cellular vulnerability of the 3xTg-AD cerebellum is described for the first time, together with its protection by scFv-h3D6. Neuron depletion in the DCN was regionally variable and followed a mediolateral axis of affectationinvolvement that was greatest in the fastigial nucleus, lesser in the interpositus, and not occurringnegligible in the dentate nucleus. Interestingly, a A sole and low intraperitoneal dose of scFv-h3D6 did protected 3xTg-AD DCN neurons from death. Further studies would providemight provide interesting information about both the potential of scFv-h3D6 as a therapeutic agent and the role of the cerebellum in AD. A u t h o r ' s d r a f t v e r s i o n 3xTg-AD mouse cerebellum protected by scFv-h3D6