title: Neural network dysfunction in Alzheimer's disease: a drug development perspective.
abstract: Over the last few years, a major focus of Alzheimer's disease research has been to understand the mechanisms by which build-up of the beta-amyloid protein (Abeta) in the brain leads to chronic neurodegeneration and eventual cell death. It is increasingly recognized that cell death is not a major cause of dementia. Indeed, recent studies suggest that Abeta causes neuritic dystrophy and interferes with mechanisms of synaptic plasticity such as long-term potentiation. There are also a number of well-described homeostatic mechanisms in the brain that help to maintain signal strength as a consequence of lowered synaptic input, which may occur as a consequence of neuritic dystrophy. This review examines mechanisms of synaptic scaling in the brain and explores prospects for future drug development based on a neural network perspective.
authors.affiliation: Menzies Research Institute, University of Tasmania, Australia. d.h.small@menzies.utas.edu.au
authors.forename: David H
authors.initials: DH
authors.lastname: Small
mesh_terms: D000544:Alzheimer Disease / Q000188:drug therapy / Q000503:physiopathology*; D000818:Animals; D016503:Drug Delivery Systems / Q000379:methods; D015195:Drug Design; D006801:Humans; D017774:Long-Term Potentiation / Q000187:drug effects; D008954:Models, Biological; D009415:Nerve Net / Q000187:drug effects / Q000503:physiopathology*