Network dysfunction in Alzheimer's disease: does synaptic scaling drive disease progression?

Accumulation of beta-amyloid protein (A beta) in the brain is a key feature of Alzheimer's disease (AD). The build-up of aggregated forms of A beta leads to synaptic loss and to cognitive dysfunction. Although the pathways controlling production and aggregation of A beta 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 alpha 7 nicotinic acetylcholine receptors (alpha 7 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.