Synaptic Impairment in Alzheimer’s Disease: A Dysregulated Symphony

AD afflicts over 35 million people throughout the world, including 5.4 million individuals in the USA alone, with a new case developing every 66 sec. Synaptic loss is the best predictor of the clinical symptoms of AD and the mechanisms by which this deficit occurs is an intense area of investigation. Aβ oligomers have been classified as types 1 and 2; the latter appears to contribute to synaptotoxicity. Tau can translocate from axons to the somatodendritic compartment and into spines, where it might interfere with synaptic function. Significant advances have been made during the past years regarding the actions, interactions, and pathological role of Aβ and tau in synapses, yet many different questions for a better understanding of how Aβ and tau are connected to impair the synaptic function remain. Alzheimer’s disease (AD) is characterized by memory loss, cognitive decline, and devastating neurodegeneration, not only as a result of the extracellular accumulation of beta-amyloid peptide (Aβ) and intracellular accumulation of tau, but also as a consequence of the dysfunction and loss of synapses. Although significant advances have been made in our understanding of the relationship of the pathological role of Aβ and tau in synapse dysfunction, several questions remain as to how Aβ and tau interdependently cause impairments in synaptic function in AD. Overall, more insight into these questions should enable researchers in this field to develop novel therapeutic targets to mitigate or delay the cognitive deficits associated with this devastating disease. Alzheimer’s disease (AD) is characterized by memory loss, cognitive decline, and devastating neurodegeneration, not only as a result of the extracellular accumulation of beta-amyloid peptide (Aβ) and intracellular accumulation of tau, but also as a consequence of the dysfunction and loss of synapses. Although significant advances have been made in our understanding of the relationship of the pathological role of Aβ and tau in synapse dysfunction, several questions remain as to how Aβ and tau interdependently cause impairments in synaptic function in AD. Overall, more insight into these questions should enable researchers in this field to develop novel therapeutic targets to mitigate or delay the cognitive deficits associated with this devastating disease.