Diagram showing Hippocampus, an area affected by Alzheimer’s Disease (credits Appendix A)
We have looked at Small and Duff’s Dual Pathway Hypothesis (DPH) of Alzheimer’s Disease in previous posts. We have also looked at the enzyme Glycogen Synthase Kinase 3 (GSK 3 or simply GSK). This is referenced in the original paper on the DPH. Here I take a closer look at the reference to GSK 3 in the original paper. This paper was published in 2008 and the science has moved along since then. Nevertheless it is still useful to get an understanding of the original reference to GSK.
In their paper Small and Duff note that there are two forms of GSK – the alpha and beta forms. They note evidence that the alpha form has been implicated in Amyloid processing but that the beta form may still be relevant. They also note that the wnt signalling pathway is an upstream regulator of GSK (remember that GSK is an upstream regulator of Amyloid and Tau processing in the DPH).
Small and Duff cite evidence that GSK is found in tangles in the Entorhinal cortex and more direct biological evidence linking GSK to Tau hyperphosphorylation. The pathways are complex as Small and Duff also reference links to the Retromer protein sorting pathway and to APOE4 as well as Presenilin involvement in the wnt signalling pathway.
Appendix A – Credits
Picture by FG Designs. Creative Commons License.
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