title: 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.
authors.affiliation: Protein Folding and Stability Group; Dpt. de Bioquímica i Biologia Molecular; Barcelona, Spain; Dpt.de Biologia Cellular; de Fisiologia i d'Immunologia; Unitat de Citologia i d'Histologia; Barcelona, Spain.
authors.forename: Gisela
authors.initials: G
authors.lastname: Esquerda-Canals
authors.forename: Joaquim
authors.initials: J
authors.lastname: Marti
authors.forename: Geovanny
authors.initials: G
authors.lastname: Rivera-Hernández
authors.forename: Lydia
authors.initials: L
authors.lastname: Giménez-Llort
authors.forename: Sandra
authors.initials: S
authors.lastname: Villegas
mesh_terms: D000544:Alzheimer Disease / Q000235:genetics / Q000378:metabolism / Q000517:prevention & control*; D016229:Amyloid beta-Peptides / Q000276:immunology*; D016564:Amyloid beta-Protein Precursor / Q000235:genetics / Q000378:metabolism; D000818:Animals; D002452:Cell Count; D002470:Cell Survival / Q000187:drug effects; D002529:Cerebellar Nuclei / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D004195:Disease Models, Animal; D005260:Female; D006801:Humans; D051379:Mice; D008822:Mice, Transgenic; D009154:Mutation; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D053764:Presenilin-1 / Q000235:genetics / Q000378:metabolism; D057127:Single-Chain Antibodies / Q000276:immunology / Q000494:pharmacology*; D016875:tau Proteins / Q000235:genetics / Q000378:metabolism
chemical_list: D016229:Amyloid beta-Peptides; D016564:Amyloid beta-Protein Precursor; D053764:Presenilin-1; D057127:Single-Chain Antibodies; D016875:tau Proteins
keywords: Alzheimer disease; DCN neurons; cerebellum; immunotherapy; scFv-h3D6