Multi-scale modeling of altered synaptic plasticity related to Amyloid β effects

As suggested by Palop and Mucke (2010) pathologically elevated β-amyloid (Aβ) impairs long term potentiation (LTP) and enhances long term depression (LTD) possible underlying mechanisms in Alzheimer's Disease (AD). In the present paper we adopt and further elaborate a phenomenological computational model of bidirectional plasticity based on the calcium control hypothesis of Shouval et al. (2002). First, to account for Aβ effects the activation function Ω was modified assuming competition between LTP and LTD, and parameter sets were identified that well describe both normal and pathological synaptic plasticity processes. Second, a biophysically plausible kinetic model of bidirectional synaptic plasticity by D'Alcantara et al. (2003) was used to support findings of the phenomenological model and to further explain underlying kinetic processes. Model fitting pointed out molecular contributors, particularly calcineurin and type 1 protein phosphatase that might contribute to observed physiological disturbances in AD.