title: Canine cognitive dysfunction and the cerebellum: acetylcholinesterase reduction, neuronal and glial changes.
abstract: The specific functional and pathological alterations observed in Alzheimer's disease are less severe in the cerebellum than in other brain areas, particularly the entorhinal cortex and hippocampus. Since dense core amyloid-beta plaque formation has been associated with an acetylcholinesterase heterogeneous nucleator action, we examined if an acetylcholinesterase imbalance was involved in cerebellum plaque deposition. By using the canine counterpart of senile dementia of the Alzheimer's type, a promising model of human brain aging and early phases of Alzheimer's disease, we investigated how cerebellar pathology and acetylcholinesterase density could be related with cognitive dysfunction. As in Alzheimer's disease, the late affectation of the cerebellum was evidenced by its lack of amyloid-beta plaque and the presence of diffuse deposition throughout all cortical grey matter layers. The highest acetylcholinesterase optic density corresponded to cerebellar islands of the granular layer and was predominantly associated with synaptic glomeruli and the somata of Golgi cells. Its reduction correlated with aging and loss of granule cells, whereas cognitive deficit only correlated with loss of Purkinje cells. The observed Bergmann glia alterations may correspond to a reactive response to the loss and damage of the Purkinje cells, their specific neuronal partner. Regarding the role of acetylcholinesterase mediation in amyloid-beta deposition, our data argue against an interaction between these two proteins because acetylcholinesterase reduction correlates with aging but not with cognitive deficit. Finally, our data support the use of companion dogs of all breeds to study aging and early phases of Alzheimer's disease.
authors.affiliation: Unitat de Bioquímica, IDIBAPS, Facultat de Medicina, Universitat de Barcelona, Barcelona, Spain.
authors.forename: Marco
authors.initials: M
authors.lastname: Pugliese
authors.forename: Carlo
authors.initials: C
authors.lastname: Gangitano
authors.forename: Sabrina
authors.initials: S
authors.lastname: Ceccariglia
authors.forename: Josep Lluís
authors.initials: JL
authors.lastname: Carrasco
authors.forename: Aurora
authors.initials: A
authors.lastname: Del Fà
authors.forename: Manuel José
authors.initials: MJ
authors.lastname: Rodríguez
authors.forename: Fabrizio
authors.initials: F
authors.lastname: Michetti
authors.forename: Joan
authors.initials: J
authors.lastname: Mascort
authors.forename: Nicole
authors.initials: N
authors.lastname: Mahy
mesh_terms: D000110:Acetylcholinesterase / Q000378:metabolism*; D000375:Aging / Q000378:metabolism / Q000473:pathology; D000544:Alzheimer Disease / Q000201:enzymology* / Q000473:pathology; D016229:Amyloid beta-Peptides / Q000378:metabolism; D000818:Animals; D002531:Cerebellum / Q000201:enzymology / Q000473:pathology*; D003072:Cognition Disorders / Q000201:enzymology / Q000473:pathology; D004195:Disease Models, Animal; D004285:Dogs; D005260:Female; D008297:Male; D009457:Neuroglia / Q000201:enzymology / Q000473:pathology; D009474:Neurons / Q000145:classification / Q000201:enzymology / Q000473:pathology; D058225:Plaque, Amyloid / Q000201:enzymology / Q000473:pathology*; D011689:Purkinje Cells / Q000201:enzymology / Q000473:pathology*
chemical_list: D016229:Amyloid beta-Peptides; D000110:Acetylcholinesterase