While this was not quantified in prior EM studies on human autopsied brain tissues, it is consistent with prior studies in cell and animal models of AD: amyloid beta reduced synaptic vesicle stores in neuronal cultures [46] and hippocampal synaptic vesicle density decreased in the presynaptic terminals in APP/PS1, 5xFAD mice and 3xTg AD mice early during the course of disease [2, 11, 58], suggesting reduced synaptic vesicles is likely an early synaptic change in human AD. Here, APP is linked to Alzheimer disease.