Microglia and myelin's role in Alzheimer’s disease

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In summary, microglia and myelin play crucial roles in the pathogenesis of Alzheimer’s disease. Microglia, the brain's resident immune cells, are involved in the inflammatory response and can either protect or damage neuronal health depending on their activation state. Myelin, which insulates nerve fibers, is essential for efficient neuronal communication; its degradation is associated with cognitive decline in Alzheimer’s. The interplay between microglial activity and myelin integrity is significant, as alterations in either can exacerbate the disease's progression, highlighting potential therapeutic targets for intervention.
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Tom.G
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From popular article at:
https://www.dailybreeze.com/2023/09...er-possible-new-cause-for-alzheimers-disease/
Microglia cleans up debris when myelin is damaged. Myelin acts as an insulator and protective covering for your brain’s nerve fibers, according to OHSU.

However, researchers found that microglia are demolished while getting rid of myelin, which is heavily rich in iron. This sabotage happens through a form of cell death named ferroptosis.
The research article, Ferroptosis of Microglia in Aging Human White Matter Injury,
is at Annals of Neurology, https://onlinelibrary.wiley.com/doi/10.1002/ana.26770

Objective​

Because the role of white matter (WM) degenerating microglia (DM) in remyelination failure is unclear, we sought to define the core features of this novel population of aging human microglia.

Interpretation​

Ferroptosis appears to be a major mechanism of WM injury in Alzheimer's disease and vascular dementia. WM DM are a novel therapeutic target to potentially reduce the impact of WM injury and myelin loss on the progression of cognitive impairment. ANN NEUROL 2023
 
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I'm confused. Microglia cleans up damaged myelin but then also itself gets damaged.
 
  • #3
Greg Bernhardt said:
I'm confused. Microglia cleans up damaged myelin but then also itself gets damaged.
A quick reading by a decidedly amateur yields --

Per paragraph 4, last sentence:
Aging human WMI in AD and VCID thus involves pronounced susceptibility to ferroptosis-mediated degeneration of iron-rich senescent microglia where lipid peroxidation injury appears to be promoted by dysfunctional microglial clearance of a high burden of myelin debris.

That seems to say:
The microglial are overloaded by heavy clean-up work, and they have been further injured by their inability to clear the extra debris. (think serious constipation!)

Cheers,
Tom

p.s. Come on you medical folks, how about some knowledgable interpretation of the article.
 
  • #4
Having lost two grandparents to it, and having seen what it does to a person, I have to say there is no other disease that scares me as much as Alzheimer's. I don't have the credentials to evaluate or even really understand this. But any research that may lead to improved understanding of the disease and potentially treatment is massively important in my book.
 
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Having lost one parent, and losing a friend to Alzheimer's, I have been collecting links. This is what I have run across in the last few years:

Why sleep and exercise can reduce risk of Alzheimer’s: Paywalled article: https://www.economist.com/science-a...ers-are-studying-the-brains-plumbing/21808465.

Healthy lifestyle has 60% lower risk of Alzheimer’s (2765 participants) over 100 related ongoing studies as of 2020: Article: https://www.nih.gov/news-events/new...le-traits-may-substantially-reduce-alzheimers.

The MIND diet reduced chances of Alzheimer’s by 53%: Article: https://www.webmd.com/alzheimers/what-to-know-about-mind-diet.

Highest to lowest quartile of lifestyle factors = 36% lower risk of dementia in large scale study: Article: https://scitechdaily.com/5-lifestyle-factors-linked-to-dementia/.

LIfestyle choices reduce chances of dementia by almost 90% in large scale ten year study:
Article: https://www.medicaldaily.com/decade...style-choices-slow-down-memory-decline-467856.
Paper: https://www.bmj.com/content/380/bmj-2022-072691.

Exercise produces hormone that protects against Alzheimer’s:
Article: https://www.medicalnewstoday.com/ar...y-help-reduce-plaque-and-tangles-in-the-brain.
Paper: https://www.cell.com/neuron/fulltex...m/retrieve/pii/S0896627323006232?showall=true.

All of which greatly helps me to motivate myself to strap on the running shoes and run 4 or 5 miles every morning at age 71.
 
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FAQ: Microglia and myelin's role in Alzheimer’s disease

What role do microglia play in Alzheimer's disease?

Microglia are the primary immune cells of the central nervous system and play a critical role in the brain's response to injury and disease. In Alzheimer's disease, microglia can become activated in response to amyloid-beta plaques and tau tangles, which are hallmarks of the disease. Activated microglia can help clear these pathological proteins but can also contribute to neuroinflammation and neuronal damage if their response is excessive or dysregulated.

How does myelin degradation contribute to Alzheimer's disease?

Myelin is the protective sheath around nerve fibers that facilitates efficient transmission of electrical signals in the brain. In Alzheimer's disease, myelin degradation can occur, leading to disrupted communication between neurons. This demyelination can exacerbate cognitive decline and other symptoms of the disease. Additionally, myelin loss can trigger further inflammatory responses by microglia, creating a vicious cycle of damage and inflammation.

Can targeting microglia be a potential therapeutic approach for Alzheimer's disease?

Yes, targeting microglia is being explored as a potential therapeutic strategy for Alzheimer's disease. Modulating microglial activity to enhance their ability to clear amyloid-beta and tau while reducing harmful inflammation could help mitigate disease progression. Various approaches, including drugs that inhibit microglial activation or promote beneficial microglial functions, are currently under investigation in preclinical and clinical studies.

What is the relationship between microglia and myelin in the context of Alzheimer's disease?

Microglia and myelin have a complex relationship in Alzheimer's disease. Microglia are involved in the maintenance and repair of myelin, but in the context of Alzheimer's, chronic activation of microglia can lead to myelin damage through inflammatory processes. Conversely, myelin degradation can activate microglia, leading to further inflammation and neuronal damage. Understanding this interplay is crucial for developing interventions that target both microglial activity and myelin integrity.

Are there any biomarkers related to microglia and myelin that can be used for early diagnosis of Alzheimer's disease?

Researchers are actively investigating biomarkers related to microglia and myelin that could aid in the early diagnosis of Alzheimer's disease. Biomarkers such as specific proteins released by activated microglia (e.g., TREM2) and indicators of myelin degradation (e.g., myelin basic protein) are being studied. Advanced imaging techniques like PET scans that can visualize microglial activation and myelin integrity are also being developed to provide early and accurate diagnosis of Alzheimer's disease.

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