Network dysfunction in Alzheimer's disease: does synaptic scaling drive disease progression?
Accumulation of beta-amyloid protein (Abeta) in the brain is a key feature of Alzheimer's disease (AD). The build-up of aggregated forms of Abeta leads to synaptic loss and to cognitive dysfunction. Although the pathways controlling production and aggregation of Abeta are well studied, the mechanisms that drive the spread of neurodegeneration in the brain are unclear. Here, the idea is presented that AD progresses as a consequence of synaptic scaling, a type of neuronal plasticity that helps maintain synaptic signal strength. Recent studies indicate that brain-derived neurotrophic factor, tumour necrosis factor-alpha and alpha7 nicotinic acetylcholine receptors (alpha7 nAChRs) regulate synaptic scaling in the AD brain. It is suggested that further studies on synaptic scaling in AD could reveal new targets for therapeutic drug development.
Small
David H
DH
Menzies Research Institute, University of Tasmania, Hobart 7000, Tasmania, Australia. d.h.small@menzies.utas.edu.au
D000544:Alzheimer Disease / Q000503:physiopathology*; D016229:Amyloid beta-Peptides / Q000378:metabolism; D000818:Animals; D003704:Dementia / Q000503:physiopathology; D018450:Disease Progression; D006706:Homeostasis; D006801:Humans; D051379:Mice; D008822:Mice, Transgenic; D008954:Models, Biological; D009415:Nerve Net / Q000503:physiopathology*; D009473:Neuronal Plasticity
D016229:Amyloid beta-Peptides