Synaptic vesicles are thought to be part of three distinct pools: the readily releasable pool (comprises approximately 5% of total vesicles), the recycling pool (about 15%), and the reserve pool (the remaining 80%). The reserve pool seems to only begin to release vesicles in response to intense stimulation. There have been several studies that suggest the reserve vesicles are seldom ever released in response to physiological stimuli which raises questions about their importance. This release in vesicles, regardless of which pool they are released from, is considered a form of short term synaptic plasticity because it is changing the functional characteristics of the presynaptic cell ultimately temporarily altering its firing properties. The difference between this and long-term potentiation is the fact that this phenomenon only occurs for the duration of time it takes to recycle and reuse neurotransmitters as opposed to it occurring over the long-term such as the characteristics underlying long-term potentiation. Further research should be conducted to identify the importance of the reserve pool vesicles in presynaptic cells. Synaptic Fatigue has not been shown to directly cause or result in a central nervous system pathology, although the degrees at which it is activated in cells has been studied as result of particular pathologies and diseases. Long-term changes in a neuron or synapse, resulting in a permanent change in a neuron's excitatory properties can cause synaptic fatigue to occur from much more or less activation that could potentially lead to some sort of physiological abnormality. Hallmarks of Alzheimer's disease (AD) are impairment of cognition, aggregation of β-amyloid peptide (Aβ), neurofibrillary degeneration, loss of neurons with accelerated atrophy of specific brain areas, and decrease of synapse number in surviving neurons. Research indicates both pre- and postsynaptic mechanisms resulting in AD. One specific abnormality includes an increased amount of presynaptic protein APP. A study was conducted where synaptic fatigue was compared between transgenic mice overexpressing APP/PS1 with their littermates who did not overexpress the protein. The results showed that fatigue was more significantly pronounced in the APP/PS1 mice, which indicates a decrease in the amount of readily releasable pools of vesicles in the presynaptic neuron. Conclusions from this study include synaptic fatigue being primarily a presynaptic phenomenon and not being affected by postsynaptic receptor desensitization, synaptic fatigue is not a result of Ca2+ ions building up in the terminal, and most importantly that synaptic fatigue is an important player and can be studied when researching the causes and effects of some neurodegenerative diseases.