Synapses and Dendritic Spines as Pathogenic Targets in Alzheimer’s Disease

Figure 1

A diagram depicting the physiological and pathological roles of Aβ. The pathway in black represents the normal function of Aβ in restraining neuronal hyperactivation. In response to neuronal activation, there is upregulation of BACE, leading to overproduction of Aβ, which then acts through LTD-related mechanism involving AMPAR removal to tune down neuronal activity. In disease condition (depicted in red), however, the excessive accumulation of Aβ leads to excessive synaptic depression and AMPAR removal, which eventually results in synapse and spine loss. Based on our unpublished work (Yu et al., manuscript submitted), we propose that Aβ can act through the LKB1→MARK→tau/PSD-95 signaling cascade to cause synapse and spine loss.