Root cause of Alzheimer's may be fat buildup in brain cells, especially in ApoE4s?

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TheresaB
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Root cause of Alzheimer's may be fat buildup in brain cells, especially in ApoE4s?

Post by TheresaB »

From this article, Root cause of Alzheimer's may be fat buildup in brain cells, research suggests published by Medical Xpress on 19 Mar 2024:
Prior research has suggested that Alzheimer's disease is caused by a buildup of beta-amyloid in plaques that grow between nerve cells. Other work has also implicated a protein called tau, which can build up in brain cells. Thus, most work involved in developing ways to prevent, slow or stop the disease is based on reducing or eliminating such buildups.
Back when Alzheimer's disease was first identified by Alois Alzheimer, he noted that in addition to the plaques and tau buildup, there was also a buildup of fat droplets in brain cells. Since that time, little effort has been made to determine whether they might be the cause of the disease.
The team wondered if the APOE variants carried different risks for developing Alzheimer's disease. To find out, they conducted a few experiments
.
They found that the brains of people with the APOE4 gene had more immune cells with a type of enzyme that boosted movement of fat droplets into brain cells. In another experiment, they found that applying amyloid to brain cells of people with the APOE4 or APOE3 variants made the cells accumulate more fat.
(I added bold font to draw focus,)

This article is based on this paper: APOE4/4 is linked to damaging lipid droplets in Alzheimer’s disease microglia published in the Journal Nature on 13 March 2024. From this paper:
In summary, we discovered that the APOE4 genotype facilitates the microglial transition to an evolutionarily conserved, maladaptive and damaging LDAM state in response to innate immune triggers including Aβ. Future studies will have to determine whether protective APOE variants operate as antagonists to this microglial LDAM [lipid droplet accumulating microglia] transition by limiting LD [lipid droplet] accumulation.
-Theresa
ApoE 4/4
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Re: Root cause of Alzheimer's may be fat buildup in brain cells, especially in ApoE4s?

Post by antimatter37 »

Looks like this is an open access paper at Nature.

https://www.nature.com/articles/s41586-024-07185-7
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Re: Root cause of Alzheimer's may be fat buildup in brain cells, especially in ApoE4s?

Post by barbS »

TheresaB wrote: Thu Mar 21, 2024 6:15 am From this article, Root cause of Alzheimer's may be fat buildup in brain cells, research suggests published by Medical Xpress on 19 Mar 2024:
Prior research has suggested that Alzheimer's disease is caused by a buildup of beta-amyloid in plaques that grow between nerve cells. Other work has also implicated a protein called tau, which can build up in brain cells. Thus, most work involved in developing ways to prevent, slow or stop the disease is based on reducing or eliminating such buildups.
Back when Alzheimer's disease was first identified by Alois Alzheimer, he noted that in addition to the plaques and tau buildup, there was also a buildup of fat droplets in brain cells. Since that time, little effort has been made to determine whether they might be the cause of the disease.
The team wondered if the APOE variants carried different risks for developing Alzheimer's disease. To find out, they conducted a few experiments
.
They found that the brains of people with the APOE4 gene had more immune cells with a type of enzyme that boosted movement of fat droplets into brain cells. In another experiment, they found that applying amyloid to brain cells of people with the APOE4 or APOE3 variants made the cells accumulate more fat.
(I added bold font to draw focus,)

This article is based on this paper: APOE4/4 is linked to damaging lipid droplets in Alzheimer’s disease microglia published in the Journal Nature on 13 March 2024. From this paper:
In summary, we discovered that the APOE4 genotype facilitates the microglial transition to an evolutionarily conserved, maladaptive and damaging LDAM state in response to innate immune triggers including Aβ. Future studies will have to determine whether protective APOE variants operate as antagonists to this microglial LDAM [lipid droplet accumulating microglia] transition by limiting LD [lipid droplet] accumulation.
I, too found an article in my news feed and looked this am -
https://healthsciences.arizona.edu/news ... alzheimers

Adding to the never ending list of hopes.
ApoE 3/4 -- rs429358(C,T), rs7412(C,C)
MTHFR A1298C
VDR Taq
all the other ++
MAO R297R MTHFD1L GAMT PEMT CCL2 SOD3 NSUDS7 ATG16L1 FOXE1 do these matter? :?: (I believe in "woo" cuz pharma never helped me)
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Re: Root cause of Alzheimer's may be fat buildup in brain cells, especially in ApoE4s?

Post by Maddog13 »

The article posted makes me wonder if the argument for statin use is valid for APOE4's? Many argue against it, yet if our brains are unable to transport lipids properly, are we better off extinguishing the lipids as much as possible?
I'm sorry if this a simpleton way of expressing it all, but I am not a science person!
-M
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Re: Root cause of Alzheimer's may be fat buildup in brain cells, especially in ApoE4s?

Post by OfficeSpace »

Maddog13 wrote: Thu Apr 25, 2024 3:13 pm The article posted makes me wonder if the argument for statin use is valid for APOE4's?
Wiki: Cholesterol, Lipids and Treatments, including statins
Or CETP inhibitors?
barbS wrote: Thu Mar 28, 2024 8:08 am Adding to the never ending list of hopes.
High-Fat Diet Linked to Alzheimer’s Through Molecular Changes summarizes recent paper Effects of a High-Fat Diet on Insulin-Related miRNAs in Plasma and Brain Tissue that seems relevant.
-Jim
ApoE ε3/ε4
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Re: Root cause of Alzheimer's may be fat buildup in brain cells, especially in ApoE4s?

Post by Maddog13 »

I've been avoiding saturated fats for sure. This sort of study would be a direct argument against those who say that a carnivore/keto diet is the answer for APOE4's.
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Re: Root cause of Alzheimer's may be fat buildup in brain cells, especially in ApoE4s?

Post by Fiver »

Hi. This is interesting, thanks for sharing. My understanding is that apoe4 on low density lipoprotein particles binds poorly to LDL receptors on the surface of fat-hungry cells. More LDL is left in circulation, hence higher “bad” cholesterol levels. Also, apoe4 interferes with the uptake of receptor bound LDL particles full of fat by disrupting endosome and lysosome pH, meaning that LDL particles aren’t digested and removed from receptors so they can be returned to the cell membranes. A traffic jam occurs. Amyloid beta is taken up by similar, nearby receptors and so the traffic jam also prevents its break down in endosomes and lysosomes, allowing it to build up outside of cells. So changing the fats in our blood might or might not be helpful; what would really help would be fixing the traffic jam. This can be done in cell culture and animals by gene therapy, replacing apoe4 with apoe2 or 3, or with certain drugs which fix the pH of these microvesicles. This is how I’ve come to understand the basic problem - as a lysosomal storage disorder. So I tend to agree that in this way “fat buildup” the problem. I hope researchers make some more progress in this area.
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