Amyloid Beta-Related Alterations to Glutamate Signaling Dynamics During Alzheimer’s Disease Progression

• Main Authors: Caleigh A. Findley, Andrzej Bartke, Kevin N. Hascup, Erin R. Hascup
• Format: Article
• Language: English
• Published: SAGE Publishing 2019-06-01
• Series: ASN Neuro
• Online Access: https://doi.org/10.1177/1759091419855541

Alzheimer’s disease (AD) ranks sixth on the Centers for Disease Control and Prevention Top 10 Leading Causes of Death list for 2016, and the Alzheimer’s Association attributes 60% to 80% of dementia cases as AD related. AD pathology hallmarks include accumulation of senile plaques and neurofibrillary tangles; however, evidence supports that soluble amyloid beta (Aβ), rather than insoluble plaques, may instigate synaptic failure. Soluble Aβ accumulation results in depression of long-term potentiation leading to cognitive deficits commonly characterized in AD. The mechanisms through which Aβ incites cognitive decline have been extensively explored, with a growing body of evidence pointing to modulation of the glutamatergic system. The period of glutamatergic hypoactivation observed alongside long-term potentiation depression and cognitive deficits in later disease stages may be the consequence of a preceding period of increased glutamatergic activity. This review will explore the Aβ-related changes to the tripartite glutamate synapse resulting in altered cell signaling throughout disease progression, ultimately culminating in oxidative stress, synaptic dysfunction, and neuronal loss.