New comprehensive review on ApoE and Alzheimer's

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broiler_x
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New comprehensive review on ApoE and Alzheimer's

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https://www.cell.com/neuron/fulltext/S0 ... 19)30083-2

This is a long, comprehensive review of ApoE and Alzheimer's that was just published in Neuron.

PDF is free!

Neuron. 2019 Mar 6;101(5):820-838. doi: 10.1016/j.neuron.2019.01.056.
A Quarter Century of APOE and Alzheimer's Disease: Progress to Date and the Path Forward.
Belloy ME1, Napolioni V1, Greicius MD2.
Department of Neurology and Neurological Sciences, FIND Lab, Stanford University, Stanford, CA 94304, USA.
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Re: New comprehensive review on ApoE and Alzheimer's

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broiler_x wrote:This is a long, comprehensive review of ApoE and Alzheimer's that was just published in Neuron.
Thanks - very nice review. Also, this is the best map I've seen of the World distribution of ApoE4. It is much different than I had imagined from other descriptions. Sub-saharan Africa has the most. Middle East has the least. Europe goes from medium in the south to higher in the north. Malaysia and Indonesia were also high. This actually makes sense when you look at early man. Originally, there was ApoE4 and early man was just in sub-Sahara Africa. The Sahara blocked travel out of Africa, but there is a 20,000 year climate wiggle, and the band of livable and unlivable areas change. Early man comes out of Africa early with just the ApoE4 allele and travel along the coast to Indonesia and also to Europe and Asia. Later, during a period when the Middle East was more green, another group came out of Africa and settled here. ApoE3 comes on the scene and provides advantage in areas with more abundance and availability of constant carbs (tubers, later farming). ApoE4 holds out in Northern Europe because of the cold and less carbs. Sub-Sahara Africa keeps its ApoE4 since most genetic mixing is out of Africa, not in. Malaysia and Indonesia keep it since it is also more isolated. The new world for the most part matches the people in Europe where they came from.
ApoE4World.PNG
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Re: New comprehensive review on ApoE and Alzheimer's

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Another interesting fact that I had not seen before - Sex makes a difference in getting AD, but only for 3/4s, not 4/4s. The Odds Ratio (OR) goes up 3-4 fold for women 3/4s over 3/3s, but it only increases 1 fold for men. There is about a 10 fold increase in the OR for both men and women 4/4s over 3/3s, with just a slightly higher rate for women than men. Oh well, so much for my male advantage :(

Also, as seen recently, there is similar amyloid between men and women, but women get more tau from Apoe4 than men.
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Re: New comprehensive review on ApoE and Alzheimer's

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Wow, that was an impressive review. Thank you for sharing.
e3/e4
No family history of AD, they drop dead of heart attacks in their early 40's!
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broiler_x
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Re: New comprehensive review on ApoE and Alzheimer's

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mike wrote: Thanks - very nice review. Also, this is the best map I've seen of the World distribution of ApoE4. It is much different than I had imagined from other descriptions. Sub-saharan Africa has the most. Middle East has the least. Europe goes from medium in the south to higher in the north. Malaysia and Indonesia were also high. This actually makes sense when you look at early man. Originally, there was ApoE4 and early man was just in sub-Sahara Africa. The Sahara blocked travel out of Africa, but there is a 20,000 year climate wiggle, and the band of livable and unlivable areas change. Early man comes out of Africa early with just the ApoE4 allele and travel along the coast to Indonesia and also to Europe and Asia. Later, during a period when the Middle East was more green, another group came out of Africa and settled here. ApoE3 comes on the scene and provides advantage in areas with more abundance and availability of constant carbs (tubers, later farming). ApoE4 holds out in Northern Europe because of the cold and less carbs. Sub-Sahara Africa keeps its ApoE4 since most genetic mixing is out of Africa, not in. Malaysia and Indonesia keep it since it is also more isolated. The new world for the most part matches the people in Europe where they came from.
I thought that map was really cool too. Your analysis is amazing. Are you an anthropologist or historian?
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Re: New comprehensive review on ApoE and Alzheimer's

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broiler_x wrote:I thought that map was really cool too. Your analysis is amazing. Are you an anthropologist or historian?
In another life, maybe. Always have been interested in both, and early man, and maps. I've been trying for months to find data to make just such a map.
Last edited by mike on Fri Mar 08, 2019 3:04 pm, edited 1 time in total.
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Re: New comprehensive review on ApoE and Alzheimer's

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Excellent review. With the extensive coverage of the lipid effect from various isoforms of APOE, I was a bit surprised that the whole mitochondrial down-regulation of E4 (manifested as a reduction in cerebral glucose utilization) was completely ignored. It’s typically considered to be a large part of the “loss of function” discussion.

I also continue to wonder about crosstalk between the CNS and peripheral APOE pools. We know HDL can traverse the BBB and can carry some degree of APOE. Perhaps the HDL that is small enough to cross the BBB is APOE depleted? Given our leakier BBBs, I can't help but wonder if that promotes more exchange between the two pools? Just speculating...

Huge thanks for sharing, broiler. I'm always encouraged to see researchers focusing specifically on our gene.
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Re: New comprehensive review on ApoE and Alzheimer's

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Julie G wrote:I was a bit surprised that the whole mitochondrial down-regulation of E4 (manifested as a reduction in cerebral glucose utilization) was completely ignored. It’s typically considered to be a large part of the “loss of function” discussion.
I also wondered about this, but then got lost in the map. They seem to be still spending most of their effort looking at AB...
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Re: New comprehensive review on ApoE and Alzheimer's

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mike wrote:
broiler_x wrote:I thought that map was really cool too.
If you are interested, here is a map showing what is believed about early man migration. The numbers on the map are when modern man got to that location. Earlier man got to Europe southeast Asia more like 700,000 years ago.
ApoE4Travel.PNG
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Re: New comprehensive review on ApoE and Alzheimer's

Post by Fiver »

Thanks for posting. I thought the first part of this was a great review. It kind of abruptly changed at the point of discussing whether or not E4 was bad from a loss of function or toxic gain of function standpoint. It's amazing that without discussing animal and cell culture models there wasn't much to say. How can we not know this? ugh.

Either way we'll know when those E4 to E3 genetic experiments in patients get going I suppose....
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