Preliminary study on CCD in canine patients: Neurofibrillary tangles and ApoE4 in combination with an antioxidant fortified diet

Abstract

Canines are known for their natural development of age-related neuropathological brain lesions, such as beta amyloid deposits as senile plaques, cerebral amyloid angiopathy and lipofuscin. Presence of these features in combination with cognitive decline and behavioral alterations is considered canine cognitive dysfunction (CCD). Studies have provided evidence of the beneficial effect of an antioxidant fortified diet in CCD patients and have connected these effects to reduced brain pathology. CCD in dogs shares similarities with Alzheimer’s disease (AD) in humans, such as beta amyloid and tau pathology. The canine has therefore been suggested as a possibly promising animal model of AD. In scientific research devoted to AD, ApoE has suggested to be an important apolipoprotein in the disease pathology. Aims of the present investigation were to expand the knowledge of CCD and to support the view of the dog as a valuable animal model of AD. First, by studying the occurrence of neurofibrillary tangles (NFT’s). NFT’s and dense content containing plaques have not been consistently demonstrated in the dog. Second, by exploring the ApoE4 immunoreactivity in dogs. From a veterinary standpoint, this study focuses on the possible correlation between the quantity of ApoE4 staining and antioxidant dietary treatment. Therefore 11 of the 12 canines available for immunohistochemistry were divided into 3 groups. One group containing old demented dogs, the second group housed the old demented dogs with dietary treatment and the third group consisted of the control dogs. Histopathological evaluation of NFT’s with the Bodian silver staining method resulted in the finding of tangles in four of the six demented dogs. Immunoreactivity of canine ApoE4 with human antibodies was found in all of the nine elderly dogs. A trend for lower ApoE4 quantities was demonstrated, with evident differences between the ApoE4 amount in the groups old demented and non-demented old control dogs. The distinction based on the ApoE4 staining in macrophages (microglia) proved significant.