“I think it would be good to know if I would get Alzheimer’s in ten years. Then I could go on a vacation before I forgot about it,” he said.
She smirked. “Don’t forget to bring a video camera.”
* * *
I find it interesting that Alzheimer’s and cholesterol uptake is governed by the same mechanism: regulated intramembrane proteolysis. This involves an enzyme cleaving a transmembrane protein so that the clipped off cytosolic portion can enter the nucleus to influence gene transcription.
But signaling mechanisms aside, I question the current models that are being used for the disease. Alzheimer’s is mostly a disease of the aged. In papers, scientists have characterized genetic mutations that cause early onset of the disease and have used mouse models that are admittedly short-lived. A vaccine that had been developed worked on the mouse model, but human trials were abruptly halted because of complications (primarily meningeoencephalitis). Maybe they should start working on proteolytic inhibitors instead.
Perhaps Alzheimer’s is a consequence of living so long. Maybe we should seriously consider a monkey model instead of a mouse model. Somebody should do a study analyzing Ab levels over time in humans. Since our brain cells don’t divide and turn over constantly like skin cells, maybe the cellular machinery wears down during aging so it can’t process the precursor to A b as efficiently. Whatever the case, I don’t think testing things out on a mouse model with the Swedish mutation of Alzheimer’s is going to have any relavence for most human patients. Not everyone has the Swedish mutation.
* * *
Talking about excess deposition, it reminds me of two strange diseases, one called scleroderma which is the production of excess collagen. The other disease causes the body to become entirely ossified (osteopetrosis?) or turned into bone. I think I read a story about it several years ago in a magazine (Time? Newsweek? The New Yorker? Harper’s?)