Alzheimer’s Disease is Not a Natural Loss of Memory

Alzheimer’s has been put on the backburner of scientific research for a majority of the 20th century. Despite similar rates of diagnoses, cancer research received about 10 times more funding than Alzheimer’s research in 2015. As Dr. Samuel Cohen points out in his TED TALK, many people associate Alzheimer’s disease with the natural process of aging; however, it is a medical disease that can be prevented.

Cohen spoke about Alzheimer’s disease in London at a TED conference in June, 2015. He began by telling the story of how Alzheimer's was discovered: in Germany, a women named Augusta was taken care of by a doctor named Alewitz Alzheimer. Augusta had all of the symptoms associated with Alzheimer’s such as confusion and inability to remember past events or people. When she passed away Dr. Alzheimer looked at her brain and found plaques, not much more was understood in 2015 about the disease than in 1901 when it was discovered.

The only starting point scientists had for research was the plaques in the brain. It was discovered that these plaques were actually bundles of misfolded proteins. Proteins are made within cells by ribosomes that assemble amino acids into long strings called polypeptides. These polypeptides then form associations and such as hydrogen and disulfide bonds with themselves and other polypeptides to create a protein. If these polypeptides form the wrong associations within each other, they are not going to function properly. These misshapen proteins can then associate with other proteins so that the proteins aggregate together and form bundles in a process called nucleation.

In Alzheimer’s disease, the specific clumps of proteins formed are called amyloid fibrils. It has been discovered that these amyloid fibrils cause that second step of Alzheimer’s called secondary nucleation. During secondary nucleation, functioning proteins come into contact with amyloid fibrils, and the fibrils cause the proteins to refold into the wrong shape and then cluster together with other misfolded proteins. These clusters of misfolded proteins are highly toxic to nerve cells and are what cause the rapid degeneration of mental processes in Alzheimer’s patients.

Cohen performed a study on mice in 2015 testing a potential drug to treat Alzheimer’s disease. Brichos is a molecule that is naturally made in the body to prevent proteins from folding the wrong way. It was found in the experiment that when brichos is applied to amyloid fibrils, it attaches to the fibrils and prevents proteins from binding to the amyloid fibrils and misfolding. This essentially prevents secondary nucleation. In Cohen’s experiment mice were treated with Amyloid beta, which are the proteins that form amyloid fibrils. When treated with brichos, the toxic clumps of proteins formed from secondary nucleation did not appear.

This is clearly promising research, yet more work needs to be done. 40 million people suffered from Alzheimer’s in 2015 yet this is expected to rise. It is believed that in the year 2050 half of people over the age of 85 will have Alzheimer’s disease.

References:

S. Cohan, et al., A molecular chaperone breaks the catalytic cycle that generates toxic Aβ oligomers. Nature Structural & Molecular Biology 22, 207–213 (2015). doi: 10.1038/nsmb.2971

Cohan, Alzheimer’s is Not Normal Aging - and We Can Cure it. TED. 2015

http://www.cam.ac.uk/research/news/molecular-inhibitor-breaks-cycle-that-leads-to-alzheimers

https://www.ted.com/talks/samuel_cohen_alzheimer_s_is_not_normal_aging_and_we_can_cure_it#t-22855