Rapamycin increases Alzheimer's-associated plaques in mice, study finds

Medical Xpress / University of Texas Health Science Center at San Antonio / JNeurosci ^ | June 7, 2022 | Manzoor Bhat, Ph.D. et al

[ConservativeMind]

Researchers have found that oral administration of rapamycin to an Alzheimer's disease mouse model causes an increase in beta (β)-amyloid protein plaques. β-amyloid buildup is a hallmark of Alzheimer's disease.

Rapamycin is approved to treat transplant and cancer patients. Publicly available data suggest that the drug might also improve learning and memory in aged mice. However, the researchers observed that after rapamycin treatment, a protein called Trem2 (triggering receptor expressed on myeloid cells 2) is dramatically diminished. Trem2 is present in microglia, which are immune cells in the brain and spinal cord.

"Trem2 is a receptor located on the surface of microglia, and it enables these cells to engulf and degrade β-amyloid," said study senior author Manzoor Bhat, Ph.D.. "Loss of Trem2 in microglia impairs the vital function of amyloid degradation, which in turn causes a buildup of β-amyloid plaques."

Previous research has shown that loss of Tsc1 leads to activation of the mTOR (mammalian target of rapamycin) signaling pathway. Rapamycin, in contrast, blocks this pathway. "We expected that selective loss of Tsc1, only in microglia and not in neurons or other cells, would have negative consequences because inhibiting mTOR with rapamycin has known therapeutic uses in some disease models," Dr. Shi said. "But the opposite was occurring." Thus, repressing Tsc1 solely in microglia to enhance β-amyloid uptake could be a potential drug target.

Findings from this study may give the medical world a reason to pause testing rapamycin on anyone at risk of Alzheimer's disease. "Rapamycin may have benefits in terms of suppressing the immune system and as a tumor suppressor," Dr. Bhat said. "But in a situation where it negatively impacts the expression of Trem2 or other critical proteins, it may have a detrimental effect. We caution that rapamycin's benefits in β-amyloid-associated Alzheimer's must be studied more carefully."

[ConservativeMind]

Rapamycin Is used by some as a supplement for enhancing brain activity.

I think this will cause them to pause a bit.

[ConservativeMind]

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[Bob434]

Dang it- i just had a great big bowl of rapamycin too!

[Nifster]

Folks self dosing

[antidemoncrat]

Most modern medicine are designed to treat a specific illness or medical condition and are usually successful but the problem is that most of them have multiple side effects, some really serious, and many doctors don’t seem to be aware of them.

[ckilmer]

I tried rapamycin once or twice. I found that it degraded my cognitive function. So I stopped.

[Oystir]

Rapamycin and the diabetes drug Metformin have been looked at being “longevity” meds. This is an interesting wrinkle, which again shows science sometimes doesn’t know what it doesn’t know, or thinks is an improvement when it is actually harmful.

[ckilmer]

People have different biologies. So the same drug can affect people in different ways. So my problem with rapamyacin could just be about me. Varied effects seems to be characteristics of all drugs.