Neuronal networks with coupling through amyloid beta: towards a theory for Alzheimer's disease

TL;DR

This paper proposes a new electrical model explaining how amyloid beta disrupts neuronal synchrony and activity in Alzheimer's disease, potentially guiding future electrophysiological studies and therapeutic approaches.

Contribution

It introduces a novel electrical model illustrating how amyloid beta affects synaptic activity and neuronal synchrony, advancing understanding of AD mechanisms.

Findings

Amyloid beta can disrupt neuronal synchrony and cause synaptic silencing.

The model aligns with experimental observations in transgenic mice.

Electrophysiological measurements of A beta could confirm its role in AD.

Abstract

Alzheimer's disease (AD) is a common form of dementia observed in the elderly due to neurodegenerative disorder and dysfunction. This arises from alterations in synaptic functioning of neurons leading to cognitive impairment and memory loss. Recent experimental studies indicate that the amyloid beta (A beta) protein, in its dimer and oligomer forms, affects the synaptic activity of neurons in the early stages of AD. However, the precise mechanism underlying A beta induced synaptic depression is still not clearly understood. In this paper, we introduce an electrical model that provides a possible mechanism for this. Our studies show that the competing effects of synaptic activity and the indirect interaction mediated by A beta, can disrupt the synchrony among neurons and severely affect the neuronal activity. This then leads to sub-threshold activity or synaptic silencing. This is in agreement with the reported disruption of cortical synaptic integration in the presence of A beta in transgenic mice. We suggest that direct electrophysiological measurements of A beta activity can establish its role in AD and the possible revival, proposed in our model. The mechanism proposed here is quite general and could account for the role of the relevant protein in other neuronal disorders also.