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ARUK 2022 | Investigating links between anti-depressants and Alzheimer’s pathology
Richard Elsworthy, PhD, University of Birmingham, Birmingham, UK, explains the rationale behind research into links between mid-life depression and Alzheimer’s disease, and also discusses research into the effects of selective serotonin reuptake inhibitors (SSRIs) on Alzheimer’s disease pathology. Dr Elsworthy discusses research which is using induced pluripotent stem cells (iPSCs), expressing various presenilin-1 mutations, to study the effects of SSRIs on the pathology of Alzheimer’s disease. Dr Elsworthy also discusses the mechanisms behind how SSRIs could affect amyloid plaque formation. This interview took place at the Alzheimer’s Research UK Conference 2022 in Brighton, UK.
Transcript (edited for clarity)
Looking at, I guess, mainly focusing in depression in Alzheimer’s disease. And, we’re interested in the increased risk with people who have midlife depression, whether that contributes to Alzheimer’s disease. And then, looking at whether people with Alzheimer’s disease also have depression, or are more at risk of having depression in late life as well. So, we’re talking to the clinicians at Birmingham...
Looking at, I guess, mainly focusing in depression in Alzheimer’s disease. And, we’re interested in the increased risk with people who have midlife depression, whether that contributes to Alzheimer’s disease. And then, looking at whether people with Alzheimer’s disease also have depression, or are more at risk of having depression in late life as well. So, we’re talking to the clinicians at Birmingham. We are interested in whether the depression is actually affecting the pathology of Alzheimer’s disease, or whether it’s a separate condition as well. And, obviously, we’re looking then at the effects of SSRIs, which are commonly prescribed for depression treatment, and how that might impact either late in life depression, or for us, it was more interesting actually, whether the antidepressants might impact the pathology of Alzheimer’s disease. And, in that case, it was APP processing as the precursor form to amyloid beta, which is one of the key pathologies. And then, also oxidative stress, which we know happens early in the Alzheimer’s disease brain as well.
So, the study sort of goes, sort of more, I guess, a bit bench side. So, moving away from people who are more into cell models. So, we’re really interested in using iPSC models, and the technology around that. So, the models that we have have different Presenilin-1 mutation and we’re looking at the effect of the SSRI, so in our case is citalopram, which is one of the more commonly prescribed SSRIs. And, we’re seeing how, whether we treat the cells over sort of an extended period of about 45 days, whether we can see a change in the pathology associated with Alzheimer’s disease there. So, with the results that we’ve got, sort of looking at around more to do with the sort of non-amyloidogenic processing. So, APP is cleaved sort of in two pathways, we get the one side that forms amyloid beta, which is the sort of pathological pathway, and on the flip side, the other side, the other pathway is involved with alpha-secretase cleavage, and releases things that are sort of beneficial for the brain.
We’re really interested in the activity of the enzymes that can actually shift that pathway towards the protective side. And, in our cell models, we’re looking in the SSRI as, actually, you can sort of shift that pathway to protective increase in the alpha-secretase enzyme, and then releasing sort of neuroprotective factors and preventing amyloid formation in the cells.