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Researchers at Massachusetts General Hospital find new mutations linked to Alzheimer’s Disease

Did you know that Alzheimer’s disease could strike as early as 40 years old in some patients? Or that the rate of Alzheimer’s —which is already the sixth leading cause of death in the U.S., according to the nonprofit Alzheimer’s Association — is steadily rising?

It is a rough wake up call, but it is true. Fortunately, a new study released on Sept. 23 from researchers at Massachusetts General

Genetics and Aging Research Unit researchers Rudolph Tanzi and Jaehong Suh at Massachusetts General Hospital found two rare gene mutations that appear to lead to late-onset Alzheimer's. PHOTO VIA FLICKR USER ROBERTGRAYATATHANDGUIDES.
Genetics and Aging Research Unit researchers Rudolph Tanzi and Jaehong Suh at Massachusetts General Hospital found two rare gene mutations that appear to lead to late-onset Alzheimer’s. PHOTO VIA FLICKR USER ROBERT GRAY AT ATHANDGUIDES.COM

Hospital in Boston identified two rare gene mutations that appear to cause late-onset Alzheimer’s Disease — the first new Alzheimer’s mutations found since 1995.

This discovery may lead to new pathways for disease prevention, said Dr. Rudolph Tanzi, the principle researcher of the study and director of the Genetics and Aging Research Unit at MGH.

“This is the first time ever we’ve found rare, disease-causing mutations for late-onset,” Tanzi said.

The Super-Cool Science Stuff
No matter what anyone says, genetics can be interesting — take it from a former biology minor — and this study is no exception.

The mutations Tanzi and his fellow Genetics and Aging Research Unit scientist Dr. Jaehong Suh found occur on a gene called ADAM10. ADAM10 codes for an enzyme, or a protein, that works as a catalyst and speeds up biological processes. The enzyme ADAM10 codes to assist in processing the amyloid precursor protein, or APP for short.

It is easiest to think of APP as just a silly little protein that is floating around, since its purpose is not terribly important in this particular study. What is important is that APP is usually cut by the enzyme that ADAM10 codes for, called alpha-secretase. When alpha-secretase cuts APP, it slices through a region of the protein called the amyloid-beta, or A-beta region. This results in a protein fragment that protects and stimulates the generation of neurons. In simpler terms, it works like a bodyguard for brain cells and it even creates new brain cells.

The mutations Tanzi and Suh found produce a different result.The mutation basically impairs ADAM10’s ability to fold correctly — yes, proteins fold. If ADAM10 does not fold correctly, beta-secretase cuts APP instead of the usual alpha-secretase. After beta-secretase cuts APP, another enzyme called gamma-secretase crashes the party and cuts one of the segments of APP again. This secondary cutting releases a ‘poison’ of sorts, called amyloid-beta, or A-beta.

A-beta is a protein that can do a lot of damage to the brain. Once ADAM10 has mutated and replicated, A-beta builds up in plaques, a typical trait of Alzheimer’s. A-beta is not only toxic to the brain, but also reduces the generation of new neurons in the hippocampus, a region of the brain essential to learning and memory, ultimately undoing Alpha-secretase’s hard work.

In short: the mutation the researchers found allows for a certain toxic protein, A-beta, to be released from a protein that normally promotes neuron health and growth.

Interpreting the research
Tanzi found the ADAM10 mutation by using lab mice. He said a previous study had shown mice whose ADAM10 activity was increased produced less of the toxic A-beta protein.

Tanzi replicated the study to ensure the results were accurate, then hypothesized that mice with the characteristic ADAM10 mutation should perform more poorly when it came to keeping their levels of A-beta low — and sure enough, that was the result the researchers saw.

Mice who were crossed with other mice who had the mutation “were about 60 percent less effective in protecting the brain against the amyloid protein” than mice without the mutation, Tanzi said.

Tanzi also said the A-beta level grows slowly in the brain with such a mutation. Because the brain is not as well equipped to protect its neurons from the toxic protein, it builds up little by little every day, eventually leading to the onset of Alzheimer’s.

The Big Picture
Tanzi, who has been studying Alzheimer’s for decades, said this discovery could have huge implications in the medical field.

“If we can figure out some way to safely elevate ADAM10 activity a little bit, that might be a way to prevent Alzheimer’s,” he said.

Though Tanzi noted this is easier said than done, this is certainly a significant step toward finding a cure. With a degenerative disease such as Alzheimer’s, the cure is really just keeping the disease from developing in the first place, Tanzi said.

Jessica Torregrossa, a Sargent College of Health and Rehabilitation Sciences freshman, said the lack of a cure for Alzheimer’s concerns her.

“Any disease that causes degeneration of either the body or the mind is very upsetting to me,” She said. “Having a lack of a cure for something is very upsetting to me, just as a future health care professional.”

Some students, such as College of Arts and Sciences junior Christopher Neil, expressed cautious optimism towards the results of the study.

“It makes me hopeful, but a lot of things enter the media that also are very hopeful, but yet don’t bear fruits as immediately as many others,” Neil said.

Neil said he feels confident researchers will eventually find a cure, but recognizes it could take “generations” to happen.

What is Alzheimer’s?
We all know Alzheimer’s disease leads to the demise of memory formation and recollection, but that is not where the problems stop.

Alzheimer’s is a form of dementia — the most common form of dementia, actually — accounting for 50 to 80 percent of such cases. Dementia is a general term for a decline in mental ability severe enough to affect everyday life, but Alzheimer’s specifically interferes with memory, thinking and behavior.

The symptoms develop slowly and get worse over time. There are currently some treatments for Alzheimer’s, but these only treat the symptoms and not the root cause of the disease. This is why Tanzi said his and Suh’s discovery is so important.

Alzheimer’s begins with subtle memory loss, especially with newly learned information, but will slowly progress to affect thoughts and behavior as well. In the later stages of the disease, sufferers may become severely confused by their surroundings or events, develop unfounded suspicions about their family and caregivers, and eventually lose motor control, which is the ability to speak, swallow or even walk.

A common misconception about Alzheimer’s is that it only occurs after the age of 65. Early-onset Alzheimer’s, however, can actually come on as early as age 40. Although early-onset is rare, only accounting for about 4 percent of adults with Alzheimer’s, it is still a reality.

While Alzheimer’s is still in its earliest stages, sufferers are usually painfully aware of its symptoms.

“My friend’s grandma has [Alzheimer’s], and she knows she has it, and knows she forgets things,” said Simone Rauch, a junior in CAS. “You don’t know if you’re going to have it when you’re older, and it’s scary to me.”

Others have a more positive outlook on the study and where it can take us to find a cure.

“I think it’s really solid research,” said Carina Traub, a sophomore in the School of Education. “I think we’re going to start getting more and more of these breakthroughs because science is getting exponentially better,” she said.

As most students recognized, a cure for Alzheimer’s Disease is still a long way off. Researchers such as Tanzi and Suh hope, however, that a cure will eventually be found with ongoing research like their own.