Microglial activation states drive glucose uptake and FDG-PET alterations in neurodegenerative diseases

[nerd]

Authors: Xiang X, Wind K, Wiedemann T, Blume T, Shi Y, Briel N, Beyer L, Biechele G, Eckenweber F, Zatcepin A, Lammich S, Ribicic S, Tahirovic S, Willem M, Deussing M, Palleis C, Rauchmann BS, Gildehaus FJ, Lindner S, Spitz C, Franzmeier N, Baumann K, Rominger A, Bartenstein P, Ziegler S, Drzezga A, Respondek G, Buerger K, Perneczky R, Levin J, Höglinger GU, Herms J, Haass C, Brendel M

Published on: October 13, 2021
pmid: 34644146
doi: 10.1126/scitranslmed.abe5640

Abstract

2-Deoxy-2-[18F]fluoro-D-glucose positron emission tomography (FDG-PET) is widely used to study cerebral glucose metabolism. Here, we investigated whether the FDG-PET signal is directly influenced by microglial glucose uptake in mouse models and patients with neurodegenerative diseases. Using a recently developed approach for cell sorting after FDG injection, we found that, at cellular resolution, microglia displayed higher glucose uptake than neurons and astrocytes. Alterations in microglial glucose uptake were responsible for both the FDG-PET signal decrease in Trem2-deficient mice and the FDG-PET signal increase in mouse models for amyloidosis. Thus, opposite microglial activation states determine the differential FDG uptake. Consistently, 12 patients with Alzheimer’s disease and 21 patients with four-repeat tauopathies also exhibited a positive association between glucose uptake and microglial activity as determined by 18F-GE-180 18-kDa translocator protein PET (TSPO-PET) in preserved brain regions, indicating that the cerebral glucose uptake in humans is also strongly influenced by microglial activity. Our findings suggest that microglia activation states are responsible for FDG-PET signal alterations in patients with neurodegenerative diseases and mouse models for amyloidosis. Microglial activation states should therefore be considered when performing FDG-PET.

 

[Pyrrhus]

Thanks for posting!

The takeaway messages from this study appear to be:


1) The currently available glucose-uptake test (FDG-PET) correlates with the neuroinflammation test (TSPO-PET):

12 patients with Alzheimer’s disease and 21 patients with four-repeat tauopathies also exhibited a positive association between glucose uptake and microglial activity as determined by 18F-GE-180 18-kDa translocator protein PET (TSPO-PET) in preserved brain regions, indicating that the cerebral glucose uptake in humans is also strongly influenced by microglial activity.

2) If you are using the FDG-PET test to look for vascular abnormalities or patterns of neuronal (dys)function in the brain, you must also consider the possibility of neuroinflammation:

Microglial activation states should therefore be considered when performing FDG-PET.

 

[nerd]

Here is the press release for the article:
In Neurodegenerative Diseases, Brain Immune Cells Have a “Ravenous Appetite” for Sugar

“The textbook view is that the signal from FDG-PET comes mainly from neurons, because they are considered the largest consumers of energy in the brain,” says Christian Haass, research group leader at DZNE and professor of biochemistry at LMU Munich. “We wanted to put this concept to the test and found that the signal actually comes predominantly from the microglia. This applies at least in the early stages of neurodegenerative disease, when nerve damage is not yet so advanced. In this case, we see that the microglia take up large amounts of sugar. This appears to be necessary to allow them for an acute, highly energy-consuming immune response. This can be directed, for example, against disease-related protein aggregates. Only in the later course of the disease does the PET signal appear to be dominated by neurons.”

 

[ljimbo423]

In Neurodegenerative Diseases, Brain Immune Cells Have a “Ravenous Appetite” for Sugar

If this is happening in ME/CFS, I wonder if this is why I get so tired and brain fogged a couple of hours after I eat. Minutes after I eat a meal, I have so much more energy and am much more clear-headed.

Now that I think about it, it seems like the opposite should be happening shouldn't it?

 

[nerd]

If this is happening in ME/CFS, I wonder if this is why I get so tired and brain fogged a couple of hours after I eat. Minutes after I eat a meal, I have so much more energy and am much more clear-headed.

Now that I think about it, it seems like the opposite should be happening shouldn't it?

When it is minutes after your meal, it might rather be the insulin-regulated metabolism you notice. I'm not sure if insulin can reach nerve cells so fast.

But I think it might be similar in ME/CFS because activated immune cells require more energy for protein synthesis. The question is if these cells are selective for glycolysis, which they probably aren't unless a pathology is involved that is specific for glycolysis-related pathways, or if any energy source suits the purpose.

I have noticed more pain since I started the ketogenic diet, and I believe this might be one reason in that ketones also saturate the energy demand - even better because of blockages in glycolysis activate faster, and the subsequent hypometabolism prevents generally hyperactive microglia from doing too much, while in ketosis, the energy source is more sustained and allows microglia to participate more in the cytokine and glutamate release cycle. This is just what I suspect, but, probably, there are other explanations as well.

The point where I feel unsure is whether microglia, like in Alzheimer's, play any physiological and protective role or if they are just rogue. Not that I really care because pain is worse than most other symptoms. Currently, I try PEA to calm down the microglia and mast cells.