Synaptic vesicle cycle and amyloid β: Biting the hand that feeds

Area of Science:

• Neuroscience
• Cell Biology
• Biochemistry

Background:

• The synaptic vesicle cycle (SVC) is essential for neurotransmission, regulating vesicle trafficking, fusion, and release at presynaptic terminals.
• The SVC links the neuronal interior to the extracellular environment, playing a role in signaling and vulnerability to pathogens.
• Alzheimer's disease is linked to amyloid beta (Aβ) production and toxicity at the synaptic vesicle cycle.

Purpose of the Study:

• To review emerging evidence on the physiological and pathological effects of amyloid beta on the synaptic vesicle cycle.
• To elucidate the mechanisms of Aβ interaction with SVC stages, including membrane recovery, trafficking, docking, and priming.
• To connect Aβ-SVC interactions with the unifying calcium hypothesis of aging and Alzheimer's disease.

Main Methods:

• Literature review and synthesis of existing research on amyloid beta and the synaptic vesicle cycle.
• Analysis of studies investigating Aβ's impact on vesicle dynamics and neurotransmitter release.
• Integration of findings within the framework of aging and Alzheimer's disease pathogenesis.

Main Results:

• Amyloid beta exerts both physiological and pathological influences on multiple stages of the synaptic vesicle cycle.
• Aβ interferes with critical processes such as vesicle trafficking, docking, priming, and fusion.
• Evidence suggests Aβ disrupts the normal functioning of presynaptic terminals.

Conclusions:

• Understanding Aβ's effects on the SVC is key to deciphering Alzheimer's disease mechanisms.
• The interplay between Aβ and the SVC offers potential novel therapeutic targets for Alzheimer's and related dementias.
• Further research into these mechanisms can illuminate fundamental presynaptic biology and aging processes.