Disruption of Long-Term Potentiation in Alzheimer’s Disease: Molecular Mechanisms and Therapeutic Solutions

Memory mechanisms such as long-term potentiation count on synaptic plasticity, the ability of connections between neurons to strengthen or weaken through excitatory and inhibitory signals. Alzheimer’s Disease (AD) is the most common cause of dementia due to its pathologies that inhibit LTP, such as amyloid-β oligomers, neurofibrillary tangles, and neuroinflammation. Studies have shown these mechanisms to damage synaptic plasticity, but the field is still very controversial regarding the approach for treatments. This paper reviews the role of LTP and LTD in normal synaptic function, how AD pathology damages this synaptic function, and the most notable treatments in the industry. The synthesized conclusion of this review is that amyloid-β, neurofibrillary tangles, and neuroinflammation are not only the main causes of deteriorated synaptic plasticity, but they can be seen as an interconnected network of pathologies that stem from each other. Understanding the true relationship among these pathologies is important for improving our understanding of AD as a whole.