Poster: Short-term Sirolimus Treatment Restores Hippocampus and Caudate Volumes and Global Cerebral Blood Flow

[WJ_PhD]

https://alz-journals.onlinelibrary.wiley.com/doi/10.1002/alz.094114

Apparently a poster from the Alzheimer’s Imaging Consortium meeting in December 2024. It
was published online on January 9th 2025.

[RapAdmin]

Result

APOE4 carriers had significantly increased Caudate and Hippocampal volumes (Fig. 1A) and gCBF (Fig. 1B) after 4 weeks of Sirolimus treatment. These differences were not found in the non-carriers (APOE3 participants). The quantitative data is shown in Table 1. It also shows that APOE4 carriers had significantly lower Hippocampal volume and gCBF at baseline compared with that of APOE3 participants (indicated by “**”), and Sirolimus tends to restore the values to closer to those of the non-carriers. No side effects were observed, and no changes in blood glucose and HbAc1 levels were found in all the participants.

Conclusion

We show that short-term Sirolimus treatment can effectively restore brain volumes and gCBF for asymptomatic APOE4 carriers. Specifically in the caudate and hippocampus, which play many roles integral in normal cognitive functioning including memory, learning, and emotional regulation, has considerable atrophy in AD. The findings imply that Sirolimus may be useful and effective to mitigate or prevent AD developments for asymptomatic APOE4 carriers.

[Elros]

Wow very exciting news, thanks for posting!

[WJ_PhD]

Yah, pretty neat findings. I did a little online sleuthing; the work is from Dr. Lin’s Lab at Univ of Missouri-Columbia and she’s done a lot of work on Alzheimers.

https://biology.missouri.edu/people/lin

" Research Summary: The goal of the Lin Brain Lab is to develop precision health approaches to prevent Alzheimer’s disease and related dementia."

Here’s current work she just published on Sirolimus and Alz. in transgenic mice with the human ApOE4 gene:

mTOR inhibition enhances synaptic and mitochondrial function in Alzheimer's...

" mTOR inhibition enhances synaptic and mitochondrial function in Alzheimer’s disease in an APOE genotype-dependent manner"

I hope the poster shows she’s moving more into human studies as well.

[BeatTheOdds]

It’s interesting that they were given 1mg per day for a month. It makes me wonder if this could be a viable strategy for longevity, at least short-term. I’ve tried various dosage regimens but never daily.

[RapAdmin]

I have to believe that this would hold true for all variants of the APOE gene, wouldn’t you think?

[AnUser]

@WJ_PhD

Dr. Lin’s Lab at Univ of Missouri-Columbia and she’s done a lot of work on Alzheimers.

Seems like the same study advertised here:

Rapamycin as a potential treatment for Alzheimer’s disease

I am in my wife’s Hybrid Prius going to the gym… and NPR is on the radio… shakes my head. And, an ad comes on the radio station for the Missouri Flagship - Big 10 University of Missouri Columbia. They are seeking clinical trial - looking for healthy people age 45 to 65 to test sirolimus for memory benefits. They pay you $1,000. You can call to participate: (573) 884-5372 Also here is a link to the website to learm more about Ai-Ling Lin, PhD: linbrain.com/clinical-trial Maybe some here are interested. Here is a video explains what they test for your potential to have Alzehiemers… for participants. Link: Paul Pepper: Prof. Ai-Ling Lin, Alzheimer's Research Study & Lois Long, Missouri Haiku Project | KBIA Scroll down for video. MU professor of radiology AI-LING LIN is looking for healthy people, aged 45-65, to participate in a research study that hopes to answer the question: “will sirolimus treatment improve MRI measures of brain function in individuals with a genetic predi…

[Agetron]

Wow… thanks for drawing my attention to Dr. Lin’s progress.

Yes, after I posted her contact information on this site, I called her and we talked for about an hour or more. She had never known of a healthy… non-organ receipient person using any dose of rapamycin. At that time, I had been on rapamycin a full 3-years - no breaks. She wanted to know about my dose - frequency of use, memory improvements… any neurological changes (like my dysphagia) , immunity concerns. Professor Lin was so curious and then I set her up with several of our Bio-med Ph.D instructors and a few neuro doctors. And then, moved on.

[medaura]

So psyched for this!

[DrRoss]

GREAT POST…glad to know about this new benefit of rapamycin.

Thanks, Ross author of: Rapamycin, mTOR, Autophagy & Treating mTOR Syndrome

[RufusDawes]

Awesome, thank you for posting! This is why is surf this site

[schotmanb]

If one takes 1mg per day for 30 days, given a half-life of about 60 days, the residual on day 30 would be around 20mg? That level likely impacts mTorC2.

[RapAdmin]

Half-life is typically quoted in research papers at around 65 hours, but that is for sick people and sometimes liquid formulations of sirolimus, and it seems to vary a lot by individual and diet.

[schotmanb]

Agreed. But, one should consider the accumulaltion aspect of taking daily doses.

[RapAdmin]

Yes - 1mg daily is on the lower end of what organ transplants take per day, and their target blood levels are 3ng/ml to 5ng/ml I think, and yes, there will be mTORC2 inhibition at that level as that is the goal with rapamycin in organ transplant patients (immune suppression).

[Karina52]

The late Dr. Alan Green was dedicated to a patient base of several hundred APOE4 carriers, about 50 of them homozygotes, whom he treated with rapamycin. Wonderful pioneer in rapamycin beyond just for longevity. He always said APOE4 patients were the most neglected patient population!

[adssx]

Discussed here: Rapamycin as a preventive intervention for Alzheimer’s disease in APOE4 carriers: targeting brain metabolic and vascular restoration - #5 by Jonas

(I should have merged the threads, didn’t see this one until now)