Figure 5

Aβ and Zn²⁺differences in AD and NDAN hippocampal synapses. A schematic summarizing the findings presented in this report. In AD there is increased Zn²⁺ in the soluble fraction compared to control and NDAN. However, both AD and NDAN have increased levels of Zn²⁺ in the synaptic vesicles (SV) which may actually reflect a storage compensatory mechanism to high Zn²⁺ levels. The reduction of ZnT3 in AD may reflect a dysfunction of this compensatory mechanism, allowing for total Zn²⁺ levels to increase. Zn²⁺ is necessary for stabilization and targeting of Aβ oligomers to the PSD. Aβ oligomers are highly associated with the PSD in AD hippocampal synapses, but are absent at NDAN synapses. This key difference could likely be due to the levels and regulation of synaptic Zn²⁺, resulting in synaptic dysfunction and cognitive decline in AD and preserved synapses and cognition in NDAN cases