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

Abstract

Accumulation of b-amyloid protein (Ab) in the brain is a key feature of Alzheimer’s disease (AD). The build-up of aggregated forms of Ab leads to synaptic loss and to cognitive dysfunction. Although the pathways controlling production and aggregation of Ab 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- a and a7 nicotinic acetylcholine receptors (a7 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.