ABSTRACT
BACE2 is homologous to BACE1, a beta-secretase that is involved in the amyloidogenic pathway of amyloid precursor protein (APP), and maps to the Down syndrome critical region of chromosome 21. Alzheimer disease neuropathology is common in Down syndrome patients at relatively early ages, and it has thus been speculated that BACE2 co-overexpression with APP would promote the early neurodegenerative phenotype. However, the in vivo function of BACE2 has not yet been elucidated. The aim of the present work has been to analyse the impact of in vivo BACE2 overexpression using a transgenic mouse model. Our results suggest that BACE2 is not involved in the amyloidogenic pathway, cognitive dysfunction or cholinergic degeneration. However, TgBACE2 animals showed increased anxiety-like behaviour along with increased numbers of noradrenergic neurones in locus coeruleus, thus suggesting an unexpected role of BACE2 overexpression.
Subject(s)
Amyloid Precursor Protein Secretases/genetics , Aspartic Acid Endopeptidases/genetics , Alzheimer Disease/enzymology , Alzheimer Disease/genetics , Animals , Anxiety/genetics , Darkness , Down Syndrome/enzymology , Down Syndrome/genetics , Gene Expression Regulation, Enzymologic , Humans , Immunohistochemistry , Locus Coeruleus/pathology , Maze Learning , Mice , Mice, Transgenic , Models, Animal , Motor Activity/genetics , Neurons/pathology , Photosensitivity Disorders/genetics , Prosencephalon/enzymology , RNA/genetics , Transcription, GeneticABSTRACT
OBJECTIVES: The aim of this study was to describe the prevalence and severity of behavioural changes associated with age and their relationship to risk factors such as sex, reproductive status, bodyweight and age. METHODS: A cross-sectional study design was chosen. A total of 325 geriatric dogs were included. Owners of dogs older than nine years were interviewed by a veterinary behaviourist. Structured phone interviews were used to gather information about four behavioural categories related to cognitive impairment: sleep/wake cycles, social interaction, learning and house training and signs of disorientation. RESULTS: Signs of cognitive impairment showed a prevalence of 22.5 per cent in geriatric dogs. Sex and age emerged as significant predictor variables. Females and neutered dogs were significantly more affected than males and entire dogs, respectively. Prevalence and severity increased with age. Although weight was not a statistically significant predictor variable, smaller animals had greater odds of showing age-related cognitive impairment. The most impaired behavioural categories were social interaction and house training. CLINICAL SIGNIFICANCE: Age-related behavioural changes should be considered by practicing veterinarians because of their relative high prevalence among geriatric dogs, especially in females.
