Role of APP and Aβ in Synaptic Physiology

Alzheimer's disease (AD) is the most common cause of dementia in aging populations. Although amyloid plaques are the hallmark of AD, loss of synapses and synaptic dysfunction are closely associated with the duration and severity of cognitive impairment in AD patients. Amyloid precursor protein (APP) and its cleavage products including A beta have been suggested as homeostatic regulators of synaptic activity. APP manipulation and A beta application, in vitro and in vivo, affect synapse formation and synaptic transmission. Moreover, synaptic dysfunction and learning deficits precede A beta plaque deposition, suggesting that synaptic alterations may underlie the initial development of the disease. Because of the pivotal role of APP and A beta in AD pathogenesis, it is essential to understand how APP and A beta modulate synaptic function. Here, we review the roles that APP and A beta play at the synapses, with particular focus on recent findings for the importance of APP in synaptogenesis and synaptic function.