While studying a protein that’s related to symptoms of Alzheimer’s disease, scientists discovered it had a close link with another protein common in cancer.
Researchers from USF, the Mayo Clinic and the Moffitt Cancer Center found a link between the cancer-related protein Akt and the protein tau.
Tau is involved with the transportation of materials inside the cell. In Alzheimer’s patients, tau becomes tangled, accumulates in the brain and kills nerve cells. It is being considered one of the hallmarks of Alzheimer’s disease.
“What we discovered is that Akt utilizes the exact same degradation pathway,” said John Koren, one of the USF researchers and a senior majoring in chemistry and microbiology. “How it gets broken down is the exact same as how tau gets broken down, and there’s a direct competition for it.”
It is this competition for breakdown that leaves the bundles of tau destroying the brain of the Alzheimer’s patient, while the body tries to get rid of the excess Akt proteins. The ideal solution would be to clear out the tangles of tau, but the Akt blocks the pathway and must be handled carefully.
“Akt itself is a significant protein throughout all cells; it’s not just a cancer-related protein,” Koren said. “There’s a lot of functioning for it in regular cells, which is one reason it’s hard to totally regulate. If you knock the whole thing out you’re going to cause damage. It’s got to be carefully regulated.”
In cancer, Akt is known to increase the longevity or survival of cancer cells.
Cancer causes cells to divide continuously, which creates tumors. This is impossible in the brain and spinal cord where neuron cells cannot divide.
“If you can’t get rid of abnormal proteins like you’re supposed to, such as is the case in Alzheimer’s disease, after awhile proteins start to accumulate in the brain and then that’s what is thought to cause the neuron loss and neurodegeneration and the memory loss,” said Chad Dickey, lead author of the study and associate professor of molecular pharmacology and physiology.
“If you can’t clear those proteins and there’s a cancer-related protein that seems to perhaps be blocking this effect, then it may show a common link between these two diseases,” he said.
Cancer and Alzheimer’s are both considered diseases of aging, Dickey said, but one is in the central nervous system in the brain and one is in the periphery.
“Evidence is emerging that’s starting to suggest that Alzheimer’s and other diseases – like Parkinson’s and Huntington’s – may actually be a form of cancer in the brain,” he said.
Their research shows a definite correlation between the two proteins during their competition for breakdown in the brain.
“It opens the door to potentially saying Alzheimer’s disease is actually a form of cancer,” Koren said. “It suggests a relationship between the two. And that only opens the door for further research.”
The research shows that it is not necessarily the presence of the Akt protein itself that causes the harm, but the amount of it.
“Everybody’s looking for a drug,” Dickey said, “but it’s possible with gene therapies that we may actually be able to find a way to lower it [Akt] which may be just as beneficial.”
Dickey stressed that while there’s no cure for most diseases, the progression can be slowed, but slowing depends on the patient and early detection.
“Do they get into the clinic right as their symptoms emerge, or do they get into the clinic four years later when they can’t remember their daughter’s name?” he said. “So there’s always going to be a need for therapies that can target at different points in that disease process.”
The study was published online Feb. 21 in the Proceedings of the National Academy of Sciences of the United States of America and supported by the Alzheimer’s Association, CurePSP, the American Federation for Aging Research and the National Institutes of Health.
“It’s a great discovery,” Koren said. “It’s somewhat scary in the sense of what it actually means; but once you start tying it together, that’s how you solve the puzzle.”