GSK in Small and Duff’s Dual Pathway Hypothesis

Stylised Diagram of the Hippocampus - Frank GaillardDiagram 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.

Index: There are indices for the TAWOP site here and here

Twitter: You can follow ‘The Amazing World of Psychiatry’ Twitter by clicking on this link.

TAWOP Channel: You can follow the TAWOP Channel on YouTube by clicking on this link.

Responses: If you have any comments, you can leave them below or alternatively e-mail

Disclaimer: The comments made here represent the opinions of the author and do not represent the profession or any body/organisation. The comments made here are not meant as a source of medical advice and those seeking medical advice are advised to consult with their own doctor. The author is not responsible for the contents of any external sites that are linked to in this blog.

Conflicts of Interest: *For potential conflicts of interest please see the About section.

One comment

  1. […] We saw in a review by Beurel and colleagues that there were two lines of evidence that focused interest on GSK3 in the research community investigating Alzheimer’s Disease and other aspects of the relationship in this post. We also looked at what Small and Duff had written about this relationship in their 2008 paper. […]


Leave a Reply

Fill in your details below or click an icon to log in: Logo

You are commenting using your account. Log Out /  Change )

Google photo

You are commenting using your Google account. Log Out /  Change )

Twitter picture

You are commenting using your Twitter account. Log Out /  Change )

Facebook photo

You are commenting using your Facebook account. Log Out /  Change )

Connecting to %s