Amyloid Beta Mutation Inhibits Presynaptic Spontaneous Release Rate and Vesicle Pool Size During Synaptic Plasticity

Alzheimer's Disease (AD) is a neurodegenerative disease that encompasses a combination of different protein mutations. Commonly studied amyloid beta mutations have the hallmark of plaques and tangles during late stages of neurodegeneration. However, amyloid beta mutations also exhibit increases in spontaneous transmission and slower protein turnover during the early stages of the disease. These early-stage molecular level changes have been proposed to lead to hyperexcitability and synaptic plasticity alterations. For example, spontaneous transmission, which is essential for both synaptic maintenance and plasticity, has been shown to be altered in the presence of amyloid beta. However, it has been difficult to disentangle the confounding effects of amyloid beta on synaptic function. Here, we utilize our entropic force model to show how amyloid beta mutations inhibit synaptic vesicle dynamics and thus spontaneous release rate dynamics during plasticity. These combined results show how molecular level changes directly lead to synapse and neuronal level functional changes.