Amyloid Beta Interference with Zinc Neurotransmission and its Possible Contribution to Neurodegeneration in Alzheimer's Disease

The amyloid beta plaques found at the synapses produce neurodegeneration in Alzheimer’s disease; therefore, we specifically look at the hippocampus in mouse tissue because of its high level of zinc neurotransmission. Amyloid beta plaques’ binding to zinc is commonly found in Alzheimer’s disease. Zinc enhances inhibitory signaling pathways and reduces excitatory signaling. Previous research has shown that with the removal of zinc, amyloid beta plaques do not localize at the synapse. Our hypothesis is that if zinc is not performing its primary function in neurotransmission, there will be an excess of excitatory neurotransmission leading to seizure activity. If neurons are receiving signaling that they do not normally receive they degenerate; we believe this neurodegeneration is caused by excessive excitatory neurotransmission. We look at the hippocampus of wild type mice and zinc knocked out mice. Zinc knocked out mice are genetically altered to not have the transporter responsible for loading zinc into the synapses to be released in neurotransmission. We look for signs of seizure activity in the hippocampus where aberrant sprouting in dentate granule cells occur. Our method is to carrying out immunohistochemistry to label synaptoporin in axons to see if the dentate granule cells are sending signals to axons (mossy fibers) in the molecular layer rather than the hilus. We predict that in the knockout mice the mossy fibers are producing aberrant sprouting in the molecular layer. We hypothesize for our continuing project that the amyloid beta interfering with Zinc neurotransmission may contribute to neurodegeneration in Alzheimer’s disease.