Neural Network Modeling of Memory Deterioration in Alzheimer's Disease

The clinical course of Alzheimer’s disease (AD) is generally character ized by progressive gradual deterioration, although large clinical variability exists. Motivated by the recent quantitative reports of synaptic changes in AD, we use a neural network model to investigate how the interplay between synaptic deletion and compensation determines the pattern of memory deterioration, a clinical hallmark of AD. Within the model we show that the deterioration of memory retrieval due to synaptic deletion can be much delayed by multiplying all the remaining synaptic weights by a common factor, which keeps the average input to each neuron at the same level. This parallels the experimental observation that the total synaptic area per unit volume (TSA) is initially preserved when synaptic deletion occurs. By using different dependencies of the compensatory factor on the amount of synaptic deletion one can define various compensation strategies, which can account for the observed variation in the severity and progression rate of AD.