What's hAPPening at synapses? The role of amyloid β-protein precursor and β-amyloid in neurological disorders

Accumulating evidence suggests that dysregulated levels of amyloid beta-protein precursor (APP) and its catabolites contribute to the impaired synaptic plasticity and seizure incidence observed in several neurological disorders, including Alzheimer's disease, fragile X syndrome, Down's syndrome, autism, epilepsy and Parkinson's disease as well as in brain injury. This review article summarizes what is known regarding the synaptic synthesis, processing and function of APP and amyloid-beta (A beta), as well as discusses how these proteins could contribute to the altered synaptic plasticity and pathology of the aforementioned disorders. In addition, APP and its proteolytic fragments are emerging as biomarkers for neurological health, and pharmacological interventions that modulate their levels, such as secretase inhibitors, passive immunotherapy against A beta and mGluR(5) antagonists, are reviewed. Molecular Psychiatry (2013) 18, 425-434; doi:10.1038/mp.2012.122; published online 28 August 2012