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Root cause of Alzheimer's may be fat buildup in brain cells, research suggests

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Re: Root cause of Alzheimer's may be fat buildup in brain cells, research suggests

#4
Doesn't this boost the hypothesis that Alzheimer's is closely related to insulin resistance in the brain? What some people call type III diabetes.

I ask because one of the hallmarks of insulin resistance is the presence of lipid droplets in close proximity to mitochondria [0].

[0] https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10455923/

Re: Root cause of Alzheimer's may be fat buildup in brain cells, research suggests

#5
I suggest changing the title to something like: "Link Between Brain Cell Fat and Alzheimer’s Could Pave the Way for Innovative Treatments". Also here is the original Nature journal reference that can be linked to instead: https://www.nature.com/articles/s41586-024-07185-7

Re: Root cause of Alzheimer's may be fat buildup in brain cells, research suggests

#7

So, is this why fasting sometimes seems like a solution? Edit: Oversimplified, but: Less, calories, less fat? Excess calories, more fat?

You should word this better. But I think Fasting helps because of autophagy, I don't think these are exactly related. I thought autophagy takes out proteins too.

Re: Root cause of Alzheimer's may be fat buildup in brain cells, research suggests

#9

Doesn't this boost the hypothesis that Alzheimer's is closely related to insulin resistance in the brain? What some people call type III diabetes. I ask because one of the hallmarks of insulin resistance is the presence of lipid droplets in close proximity to mitochondria [0]. [0] https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10455923/

Here's what the authors speculate [1],

> A recent report showed that innate immune triggers (for example, Escherichia coli and Salmonella) induce LD formation in peripheral macrophages as part of an evolutionarily conserved antimicrobial defence in which LDs coated with antimicrobial proteins, such as cathelicidin (CAMP), kill bacteria8. We speculate that a similar programme can be triggered in human microglia exposed to Aβ, LPS and other innate immune activators and disrupt brain homeostasis. Protein aggregates found in other neurodegenerative diseases may trigger the LDAM state. For example, alpha-synuclein binding to TLR2 and TLR5 induces microglial NLRP3 inflammasome activation, which is a shared signature seen in LDAM36. Given that we recently identified that LDAM are abundant in the ageing mouse brain, LDAMs may also be triggered by hitherto unknown protein aggregates and innate immune activators which accumulate with age. Interestingly, the most enriched pathway in human LD-containing iMGs is ‘cellular senescence’, similar to lipid-laden ‘foamy macrophages’ in atherosclerosis which have a senescent phenotype and are drivers of pathology37. Perhaps in the natural ageing of various organs, LD-accumulating tissue-resident macrophages represent a general class of senescent myeloid cells which are drivers of tissue inflammation.

It could be a lot of things, and there might be multiple pathways that lead to this state.

[1] https://www.nature.com/articles/s41586-024-07185-7#Sec6

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