Synaptic degeneration in Alzheimer disease

Alzheimer disease (AD) is characterized by progressive cognitive decline in older individuals accompanied by the presence of two pathological protein aggregates - amyloid-beta and phosphorylated tau - in the brain. The disease results in brain atrophy caused by neuronal loss and synapse degeneration. Synaptic loss strongly correlates with cognitive decline in both humans and animal models of AD. Indeed, evidence suggests that soluble forms of amyloid-beta and tau can cause synaptotoxicity and spread through neural circuits. These pathological changes are accompanied by an altered phenotype in the glial cells of the brain - one hypothesis is that glia excessively ingest synapses and modulate the trans-synaptic spread of pathology. To date, effective therapies for the treatment or prevention of AD are lacking, but understanding how synaptic degeneration occurs will be essential for the development of new interventions. Here, we highlight the mechanisms through which synapses degenerate in the AD brain, and discuss key questions that still need to be answered. We also cover the ways in which our understanding of the mechanisms of synaptic degeneration is leading to new therapeutic approaches for AD.

Automated summary

Alzheimer's disease is a neurodegenerative disorder characterized by cognitive decline and the presence of amyloid-beta and tau protein aggregates in the brain. Synaptic loss plays a crucial role in cognitive decline, and the spread of pathology is mediated by soluble forms of amyloid-beta and tau. Understanding the mechanisms of synaptic degeneration is essential for developing new therapeutic approaches for Alzheimer's disease.