Mechanisms of Synaptic Homeostasis in Alzheimer's Disease

Despite considerable progress in defining the role of the β-amyloid protein (Aβ) in the pathogenesis of Alzheimer's disease (AD), the mechanism by which accumulation of Aβ causes dementia remains elusive. Memory loss is probably caused by an Aβ-induced change in synaptic plasticity. Computational neuroscience (neural network modelling) studies demonstrate that cell death (or synaptic loss as a consequence of cell death) per se cannot cause the specific pattern of gradual amnesia that occurs in AD. Amnesia typical of that seen in AD can only be produced when synaptic scaling occurs. Synaptic scaling is a compensatory homeostatic mechanism which maintains the excitatory response of individual neurons and prevents the catastrophic amnesia associated with synapse loss. In this review, several possible mechanisms of synaptic scaling are described.