Sleep-wake states in transgenic mouse models overexpressing the human beta-amyloid precursor protein

Studies testing the amyloid hypothesis and recent advances in mouse molecular genetic technologies have played a critical role in improving our understanding of Alzheimer's disease (AD). Mouse models of AD currently available show only some of the characteristic neuropathology in human AD. Studies have demonstrated, however, that these models are excellent tools for characterizing different aspects of the molecular pathology of AD and the neurobiological basis for the clinical heterogeneity in AD. The present discussion focuses on behavioral and physiological data obtained in transgenic (Tg) mice overexpressing the mutant human beta-amyloid precursor protein (hbetaAPP). This mouse model exhibits memory and neurophysiological deficits at ages preceding amyloid-beta-peptide (Abeta) plaque formation that worsened with age and Abeta plaque formation. In spite of these findings, very little emphasis has been placed on characterizing the neurobiological basis of the diverse neuropsychiatric symptoms that are also observed in AD, including sleep disturbances. Taking into consideration the relationship between memory processes and sleep, the use of animal models of AD as a preclinical bioassay has the potential to characterize the neural substrates mediating clinical manifestations of AD, such as sleep-wake states, and contribute to the development of treatments for early stages of AD.