Loss of deep cerebellar nuclei neurons in the 3xTg-AD mice and protection by an anti-amyloid β antibody fragment

Abstract

The therapeutic potential of scFv-h3D6 has recently been shown in the 3xTg-AD mice. A clear effect on amyloid β (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 involvement that was greatest in the fastigial nucleus, lesser in the interpositus and negligible in the dentate nucleus. A sole and low intraperitoneal dose of scFv-h3D6 protected 3xTg-AD DCN neurons from death. Further studies might provide interesting information about both the potential of scFv-h3D6 as a therapeutic agent and the role of the cerebellum in AD.

Keywords: :

• scFv-h3D6
• immunotherapy
• Alzheimer disease
• cerebellum
• DCN neurons

Disclosure of Potential Conflicts of Interest

No potential conflict of interest was disclosed.

Acknowledgments

The animals used in the present study come from the colony of homozygous 3xTg-AD and wild-type NTg mice established by Lydia Giménez-Llort at the Universitat Autònoma de Barcelona, Spain, from progenitors kindly provided by Frank M. LaFerla, Department of Neurobiology and Behavior, University of California Irvine, California, USA. This work was supported by FMM-2008; FISPI10–00975, -00265 and -00283; SGR2009–00761 and -42271. G.R-H is supported by a MAEC-AECI fellowship (Spanish government) and G.E-C. by a PIF (UAB, Spain) fellowship.

Notes

† These authors contributed equally to this work.