Longitudinal study of spatial learning in the PDAPP mouse

Abstract

Dementia is a psychiatric disorder of old age. Alzheimer's Disease (AD) is the most common form, accounting for 50-70% of all cases. In Western Europe, approximately 5% of the population over 60 years of age are affected, and this rises to 20% of the population aged 80 years or over. With the increase in the average length of life due to medical advances, the size of the aged population is rising and globally may number 1 billion by 2025. Thus, the number of AD cases is set to increase dramatically.

One approach to understanding a disease is to model it. This allows specific predictions to be tested and novel information about the basic mechanisms, cause, onset and progression of the disease to be elucidated. Recently, several transgenic mouse models of AD have been developed. One such model, the PDAPP mouse, shows AD-like pathology. The transgene is human amyloid precursor protein (APP), a protein implicated in AD, with a mutation found in families with inherited AD.

Spatial memory was investigated in this model as it is hippocampal dependent/ and the hippocampal formation is one of the earliest areas to be affected by AD. A longitudinal study in the watermaze was undertaken to follow the performance of the animals as they aged. A delayed matching to place protocol· was used due to repeated testing of the same animals at different ages.

PDAPP animals were impaired relative to littermate controls at the earliest age tested, and this deficit persisted as the animals aged. Consequently, no age-dependent deficit was observed. Mere overexpression of the transgene may be enough to cause a deficit in spatial learning, although the task may yet be improved in sensitivity to reveal an age-related change in performance.