"We already knew activated microglia and astrocytes were major villains in Alzheimer’s"
This does not seem at all sure.
They are both involved with blocking invaders from reaching brain.
So if at old age immune system starts failing and bugs get through blood brain barrier, symptoms would match with that (and famous amyloid plagues are also defense mechanism against bugs).
That way, the analysis might be less affected by any potential differences in cell type proportions. You might have already done this though, or I might be confused about how their tool works. And even this way, the analysis would probably still be affected by differences in sub-cell type proportions. Since it's difficult to define a cell "type", so sub-cell types proportion differences end up being a major factor in this type of analysis, in my experience.
Thank you very much for this overview, I didn't know about this tool. I played a little with it already and expect to do much more with this or similar datasets in the future
Another possible speculation: are neurons becoming more like astrocytes/microglia because they’re switching to directly utilizing glucose as fuel instead of lactate?
"We already knew activated microglia and astrocytes were major villains in Alzheimer’s"
This does not seem at all sure.
They are both involved with blocking invaders from reaching brain.
So if at old age immune system starts failing and bugs get through blood brain barrier, symptoms would match with that (and famous amyloid plagues are also defense mechanism against bugs).
Awesome tool and interesting analysis! I'm not sure if you already did this, but if not, perhaps another way to do this analysis is to specify the cell type you are interested in doing the comparison within. For example, something like this for neurons: https://www.dropbox.com/scl/fi/72lgyngiqwd0zgumczl3y/cellxgene_example.png?rlkey=djn85md0jgbwpamlj2vlq35tm&e=1&dl=0
That way, the analysis might be less affected by any potential differences in cell type proportions. You might have already done this though, or I might be confused about how their tool works. And even this way, the analysis would probably still be affected by differences in sub-cell type proportions. Since it's difficult to define a cell "type", so sub-cell types proportion differences end up being a major factor in this type of analysis, in my experience.
I did that, got pretty much the same results restricting to neurons
Thank you very much for this overview, I didn't know about this tool. I played a little with it already and expect to do much more with this or similar datasets in the future
Another possible speculation: are neurons becoming more like astrocytes/microglia because they’re switching to directly utilizing glucose as fuel instead of lactate?
So cool! Thanks for sharing!