Expression Analysis Finds Three Distinct Types of Alzheimer’s

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SusanJ
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Expression Analysis Finds Three Distinct Types of Alzheimer’s

Postby SusanJ » Sat Jan 16, 2021 10:04 am

If you have read his books, you will be familiar with Dr. Bredesen's different types of AD.

Here we have some molecular research that shows that what actually happens in the brain can be characterized by different gene expression profiles and molecular drivers. The end results show differences in plaque, tangles and neuroinflammation for each type.

"One of these, dubbed type C, fit a classic Alzheimer’s pathological profile, with numerous plaques and tangles as well as neuroinflammation. In types A and B, however, tau pathology predominated, with fewer plaques evident. Type A was distinguished by neuronal hyperexcitability, B by loss of oligodendrocytes. At a more granular level, B and C could be broken down further into two related groups, for a total of five molecular subtypes."

And yes, ApoE status was linked to the different types.

"The scientists subdivided Type C into two subtypes, C1 and C2. At a genetic level, C1 was more likely than the other subtypes to be found in APOE4 carriers; this allele associates with plaque burden and AD risk. Conversely, C2 was not enriched among APOE4 carriers. Overall, this subtype had fewer expression changes than did C1, with Aβ and apoptosis gene pathways the same as in control brain."

This seems like some groundbreaking work, which could be helpful in both creating new diagnostic markers and individualizing treatment plans.

"Researchers agreed on the need for new fluid biomarkers to distinguish subtypes. The current ATN markers of amyloid, tau, and NfL cannot capture the complexity of the disease, Seyfried said. Zhang plans to incorporate peripheral biomarkers and clinical features into the characterization of his subtypes."

Would be interesting to see if this could be mapped to Bredesen's types and treatments.

https://www.alzforum.org/news/research- ... alzheimers

Family Tree Guy
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Re: Expression Analysis Finds Three Distinct Types of Alzheimer’s

Postby Family Tree Guy » Tue Jan 19, 2021 7:39 pm

@SusanJ- thank you for posting. This is an interesting study and the scientific literature is seeing more of these types of research projects. One thing that I am struck by these days- describing different sub-types of Alzheimer's may or may not end up being useful. Observing heterogenous symptoms and biology for the same disease is actually quite normal for infectious diseases. Just look at Covid- it is the same virus that causes some to have no symptoms, others mild, others severe.

In a nutshell, I read this research and think it could be adding to the potential evidence of pathogen causation of AD, vs. 3 distinct diseases...

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SusanJ
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Re: Expression Analysis Finds Three Distinct Types of Alzheimer’s

Postby SusanJ » Wed Jan 20, 2021 5:07 pm

Family Tree Guy wrote:In a nutshell, I read this research and think it could be adding to the potential evidence of pathogen causation of AD, vs. 3 distinct diseases...


Interesting take. When I first read it, I thought, not so much 3 distinct diseases, but that maybe we'll have a more personalized approach to treatment based on the different gene expression profiles and molecular drivers.

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Re: Expression Analysis Finds Three Distinct Types of Alzheimer’s

Postby Family Tree Guy » Wed Jan 20, 2021 6:18 pm

SusanJ wrote:Interesting take. When I first read it, I thought, not so much 3 distinct diseases, but that maybe we'll have a more personalized approach to treatment based on the different gene expression profiles and molecular drivers.


I am rooting for Cortexyme, whose ph3 clinical trial will readout in December 2021, assuming all goes well. They are testing their gingipain inhibitor (the virulence factor secreted by P. gingivalis). 2/3rd of their ~640 patients are E4 carriers. The part of the story / theory that I find amazing is that the gingipains preferentially attack the apilipoproteinE coded for by the E4 allele, and to a much lesser degree the E3. The gingipains do not harm E2 at all. So while there is much more to the overall theory, it comes down to gene + bacterium = Alzheimer's.

My hope is that cognitive function is restored to some degree as Alzheimer's patients have more functional apilipoproteinE in their cells, rather than the fragments that the gingipains cause.

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Re: Expression Analysis Finds Three Distinct Types of Alzheimer’s

Postby SusanJ » Wed Jan 20, 2021 8:49 pm

Family Tree Guy wrote:My hope is that cognitive function is restored to some degree as Alzheimer's patients have more functional apilipoproteinE in their cells, rather than the fragments that the gingipains cause.


Thanks for sharing. Will be interesting to see where that research goes!


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