BrainStorm Live Episode 19: What Role Does ApoE4 Play in Alzheimer’s Disease?
Amprion’s CEO Dr. Russ Lebovitz discusses the role ApoE4 plays in Alzheimer’s disease, and how ApoE4 facilitates the misfolding of Abeta and Tau proteins associated with Alzheimer’s.
Does ApoE4 play a role with Abeta or Tau and could it be a risk factor for Alzheimer’s?
At Amprion, we clearly believe that misfolded, small, soluble aggregates of Abeta, Tau, and Synuclein are the cause and the particles that maintain the disease.
How does this ApoE4 relate to misfolded Abeta, Tau, and Synuclein, and how does that help understand the role of these particles and ApoE4 together in increasing the risk of the disease?
So, again, Alzheimer’s appears to be caused by misfolding of Abeta, which then goes on to cause a number of other things, one of which is neurodegeneration, the formation of plaque.
ApoE4 was found early on to be a protein that can also misfold in a similar manner to Abeta, and Tau, and Synuclein, and in fact, several scientists have shown that in patients with Alzheimer’s, when they took the plaque out from the brain and looked for the proteins, it was predominantly Abeta, but there was misfolded ApoE4 in those plaques as well, suggesting that ApoE4 may interact with Abeta to help misfold, and it may facilitate this misfolding and speed up the progression of the disease.
Very recently, the other protein that appears to be very important in Alzheimer’s, and also in a number of cognitive neurodegenerative disease, called Tau, in the last few months, we’ve seen several manuscripts and pieces of very convincing work that ApoE4 binds to Tau and may facilitate the misfolding of Tau also. Even in the absence of Abeta, ApoE4 seems to interact directly with Tau, and to facilitate misfolding of both Abeta and Tau.
Does ApoE4 play a role with Synuclein and could it also be a risk factor for Parkinson’s?
I believe that, genetically, there’s not nearly as much evidence that ApoE4 is associated with Parkinson’s, and so, right now, we don’t know whether ApoE4 plays a role in helping to misfold Alpha Synuclein. If we find that that’s true, then we may find also a link between ApoE4 and Parkinson’s, but it’s possible that there are other genes that form proteins that can misfold, and they may co-misfold with Synuclein in the way ApoE4 does with Abeta and Tau. So, I’d say that, you know, right now it is unknown if there’s a role for ApoE4 in Parkinson’s, but very clearly a role for ApoE4 in the misfolding of both Abeta and Tau.
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