My Introduction to Rapamycin

Getting serious about AD prevention!

In the early days of researching APOE4, I stumbled across the website of Dr. Alan Green, a physician based in Little Neck, NY. His approach was bold, and to me—deeply hopeful. Dr. Green believed that Alzheimer’s Disease could be prevented in APOE4 carriers through the off-label use of rapamycin (also known as sirolimus), a drug traditionally prescribed to organ transplant recipients.

Since 2017, he had focused his practice exclusively on this high-risk population. His patient base included over 700 individuals with the APOE4 gene, nearly 150 of them homozygous (4/4)—those at the highest known genetic risk. Yet, according to Dr. Green, none of his patients had shown signs of memory loss. He was convinced that, with a healthy lifestyle and once-weekly rapamycin, they could remain cognitively intact for life.

I picked up the phone and left a message. To my surprise, he called me back within minutes. We had a lively and encouraging conversation that ended with my booking a flight to New York to meet him in person. I wanted to become his patient—and begin my own rapamycin journey.

That was four years ago!

Dr. Alan Green

At the time, taking an mTOR inhibitor like rapamycin off-label felt like stepping into unknown territory. It was widely known for its use in organ transplant recipients to prevent rejection, not as a longevity drug or Alzheimer’s preventative. But I was 69, carrying two copies of APOE4, and I felt the risk of doing nothing was far greater than the risk of doing something.

After my visit with Dr. Green, I wrote a quick summary of our meeting (linked below if you’re curious). He explained his working theory: that APOE4 damages the brain’s protective barrier by impairing the cerebrovascular system via cyclophilin A (CypA)—a mechanism that weakens blood-brain barrier (BBB) integrity in pericytes. His hypothesis drew heavily from the work of Dr. Berislav Zlokovic, a renowned Alzheimer's researcher.

Summary of Visit to Dr. Alan Green, Nov. 2021

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Includes protocol and references

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Although Dr. Zlokovic is currently on extended leave due to unrelated scientific misconduct allegations, the core findings around APOE4-induced BBB breakdown have since been independently replicated by multiple labs and remain scientifically valid.

Rapamycin, meanwhile, has emerged as one of the most exciting compounds in the longevity and biohacking world—widely studied for its potential to extend lifespan and delay age-related disease. The common off-label protocol is 6 mg once weekly, though some adjust based on labs or side effects. Dr. Green believed that every APOE4 carrier should be taking rapamycin starting at mid-life. (women after menopause/childbearing).

He was always careful and practical. Along with my rapamycin prescription, he gave me a Z-Pak (azithromycin) and instructed me to take it if I ever developed an infection. Rapamycin can suppress our bodies innate ability to fight bacterial infections efficiently. Four years later, I’ve never needed to use the Z-Pak. The only side effect I’ve noticed on rapamycin is occasionally low lymphocyte count, which I manage by skipping a week or spacing doses to every 9–10 days at different intervals. Dr. Green also introduced me to off-label Dasatinib. I’ll share that another day.

Then, in September 2024, I received the very sad news that Dr. Green had passed away. I knew he was in hospital and sent him an email wishing him well and a speedy recovery. He responded to my message but just a few days later, I heard he was gone!

He was a trailblazer—a humble, kind, brilliant man ahead of his time. I am deeply grateful to have known him and to have been under his care. After our in-person visit in New York, we kept in touch through biannual Zoom consultations. He was always gracious, generous with his time, and—without fail—delightful to talk to.

Thankfully, Dr. Green’s website is still active, and it remains one of the most informative resources available on rapamycin, Alzheimer’s prevention, and APOE4.

If you want to learn more about rapamycin, there is extensive information to be found at rapamycin.news including resources such as sourcing, loads of FAQs and more. I’d also like to refer you to a splendid Harvey Schwartz, MD podcast with Prof. Arlan Richardson, Phd, Biochemist and Geriatric Medicine on rapamycin.

🔬 Supporting Studies
Biomedcentral
Pubmed
Frontiersin

For quick takes and live updates (APOE4 in the News) and more, follow my notes!

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