Synaptic basis of Alzheimer's disease: Focus on synaptic amyloid beta, P-tau and mitochondria

Alzheimer's disease (AD) is a progressive and synaptic failure disease. Despite the many years of research, AD still harbors many secrets. As more of the world's population grows older, researchers are striving to find greater information on disease progression and pathogenesis. Identifying and treating the markers of this disease, or better yet, preventing it all together, are the hopes of those investing in this field of study. Several years of research revealed that synaptic pathology and mitochondrial oxidative damage are early events in disease progression. Loss of synapses and synaptic damage are the best correlates of cognitive deficits found in AD patients. As the disease progresses, there are significant changes at the synapse. These changes can both shed greater light onto the progression of the disease and serve as markers and therapeutic targets. This article addresses the mechanisms of synaptic action, mitochondrial regulation/dysregulation, resulting synaptic changes caused by amyloid beta and phosphorylated tau in AD progression. This article also highlights recent developments of risk factors, genetics and ApoE4 involvement, factors related to synaptic damage and loss, mislocalization of amyloid beta and phosphorylated tau, mitophagy, microglial activation and synapse-based therapies in AD. Furthermore, impairments in LTD and reactivation of microglia are discussed.

Automated summary

Alzheimer's disease is a progressive disease associated with synaptic dysfunction, with researchers striving to find more information on disease progression and pathogenesis. Synaptic pathology and mitochondrial oxidative damage are early events in the progression of AD, with synaptic loss and damage being key correlates of cognitive deficits in patients. As the disease advances, significant changes occur at the synapse, shedding light on the disease progression and serving as potential markers and therapeutic targets.