Transgenic animals relevant to Alzheimer's disease

This article reviews the functional studies that have been carried out on transgenic and knockout animals that are relevant to Alzheimer's disease (AD). The discussion focuses upon the functional characterisation of these strains, particularly upon factors that affect synaptic processes that are thought to contribute to memory formation, including hippocampal long-term potentiation. We examine the use of transgenes associated with amyloid precursor protein and presenilin-1, their mutations linked to early onset familial AD, and the recent attempts to establish double transgenic strains that have an AD-like pathology which occurs with a more rapid onset. The development of new transgenic strains relevant to Alzheimer's disease has rapidly outpaced their characterisation for functional deficits in synaptic plasticity. To date most studies have focused on those transgenes linked to the minority of familial early onset rather than late-onset sporadic AD cases, and have focused on those changes linked to the induction of the early-phase of hippocampal long-term potentiation. Future studies will need to address the question of whether the development of AD pathology can be reversed or at least halted and this will be aided by the use of conditional transgenics in which genes linked to AD can either be switched on or off later in development. Furthermore, it remains to be resolved whether the deficits in synaptic function are specific to the hippocampus and whether deficits affect late-phase long-term potentiation. Nonetheless, the recent advances in genome sciences and the development of transgenic technology have provided a unique opportunity to study how genes associated with human cognitive dysfunction alter synaptic transmission between neurones in the mammalian brain.