""" MEG3 (maternally expressed 3) is a maternally expressed, imprinted long non-coding RNA gene.[3] At least 12 different isoforms of MEG3 are generated by alternative splicing.[4] Expression of MEG3 is lost in cancer cells.[4][5] It acts as a growth suppressor in tumour cells, and activates p53. """ (enwiki)

So, you can potentially trade higher risk of cancer for disabling a programmed cell explosion pathway taken in Alzheimer's. That seems interesting.

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To go on a slight tangent, I'm still confused why all the attempts at clearing amyloid plaque don't stop progression of the disease, and yet pharma continues to invest massive effort in the hypothesis, developping yet more amyloid drugs

But somehow we rarely hear about effort into the tau tangles themselves in popsci articles. I don't know if other targets like tau are just too hard to investigate, or if funding is really slow to shift and we're bound to spend 30 years pouring money in an old idea that invariably yields nothing in clinical trials

> I'm still confused why all the attempts at clearing amyloid plaque don't stop progression of the disease

Newer drugs aimed at inhibiting amyloid-beta plaque formation in early-stage Alzheimer’s disease are showing an effect. There’s a long ways to go, but it doesn’t look like the amyloid-beta theory is dead. There is likely something there.

https://en.wikipedia.org/wiki/Lecanemab

> [...] human brain cells were transplanted into the brains of genetically modified mice.

The discovery is that MEG3 is the molecule that is expressed when amyloid plaques form. It signals the neurons to kill themselves.

Here's the paper:

MEG3 activates necroptosis in human neuron xenografts modeling Alzheimer’s disease

https://www.science.org/doi/10.1126/science.abp9556

> The human neurons, but not the mouse neurons, displayed severe Alzheimer’s pathology, including tangles and necroptosis. Human neurons up-regulated the neuron-specific maternally expressed gene 3 (MEG3) in response to amyloid plaques.