Scientists just took a major step forward in understanding Alzheimer's

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How to Reduce Your Risk Of Alzheimer's Disease
Alzheimer's
is a terrible disease that is slowly damaging the brains of an estimated 5.3 million Americans, most of them over age 65, according to the Alzheimer's Association.

Scientists know that a protein called amyloid builds up in the brains of people with Alzheimer's, and the clumps of amyloid are likely responsible for the brain damage that makes people with the disease lose their memory, become disoriented in time and space, and have other thinking, mood, and behavioral problems.

Until now, scientists had pieced together what they know about how Alzheimer's progresses by comparing people at different stages of the disease to each other.

But to really verify what scientists think is going on — particularly the relationship between amyloid and the development of Alzheimer's symptoms — scientists would need to closely follow the disease's progression from the very beginning in individuals. That's been very difficult, in part, because usually by the time someone is showing symptoms, the disease is already well underway.

A new paper from Wai-Ying Wendy Yau and colleagues at the University of Pittsburgh, published in The Lancet Neurology, is just the sort of study of individuals with Alzheimer's that scientists had been missing. The experiment is very small and the findings are preliminary, but the study's design allowed scientists to examine the progression of disease more closely than ever before.

Tracking changes in the brain

The new study followed seven individuals who had genetic mutations that are all but guaranteed to cause Alzheimer's; they're responsible for less than 5% of cases. Alzheimer's has a complex and partially unknown matrix of causes, but following this subset of patients let researchers track people they knew would eventually develop the disease, even before they were symptomatic.

Over a period of between six to eleven years, the scientists measured the amount of amyloid collecting in the brain of each patient, the extent of their brain damage, and their scores on a test of brain function. With this information, the scientists could track how Alzheimer's progressed in an individual patient for a longer period of time than they ever have before.

The graph below summarizes what they found.

The red line represents amyloid building up in the brain, which increases over time. The green and blue lines stand for two different factors that reflect the neurodegeneration, or progressive brain damage, Alzheimer's causes. As they go up, that indicates the brain is getting more and more damaged. The graph's purple line is for a measure of cognition, and the way it goes up shows when in the course of Alzheimer's disease a person's ability to think and remember gets worse:

alz_progression_graph


Here's what all that means: Many years before any symptoms of Alzheimer's show up, amyloid has already begun to build up in the brain. Progressive brain damage and the various symptoms of the disease only show up after the amount of amyloid in the brain has stabilized.

In other words, the scientists saw Alzheimer's progressing in three stages:

  1. Amyloid builds up gradually.
  2. Amyloid stops building up, but what's already in the brain doesn't go away.
  3. Gradual brain damage starts and causes the symptoms of Alzheimer's like memory loss and confusion.

Previously, scientists had basically thought stages 1 and 3 overlapped, with no stage 2 separating them.

Caveats and next steps

brain alzheimer's beta-amyloid plaques










(Photo credit Lawrence Berkeley National Laboratory)

​The scientists note that these findings need to be verified in a study of more patients (they only looked at seven in this experiment). Furthermore, it's not a given that Alzheimer's disease progresses the same way in people with the mutations as it does in the general public.

But this study is a step towards being able to detect Alzheimer's early and monitor how it progresses more reliably than we can now, Giovanni Frisoni and Pieter Jelle Visser write in a commentary on the paper in The Lancet Neurology.

This would be really helpful in the search for a treatment for the disease, because when scientists can monitor disease progression during a clinical trial, they know sooner whether the treatment being tested is actually working. To be able to do that, they need a clear picture of how the disease progresses when it's not treated.

An effective treatment for Alzheimer's is still likely a long way off, but this crucial step in understanding the disease is, as Frisoni and Visser say, "much needed."

See some notable people who were diagnosed with Alzheimer's:

13 PHOTOS
Notable people with Alzheimer's
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Scientists just took a major step forward in understanding Alzheimer's
This file photo dated 04 November, 1991 shows US President Ronald Reagan giving a speech at the dedication of the library bearing his name in Simi Valley, California. He was US president from 1981 to 1989 and retreated from public life after it was revealed he was suffering from Alzheimer's disease. (Photo by J. David Ake, AFP/Getty Images)
In this Jan. 28, 2013, file photo, Tennessee head coach emeritus Pat Summitt smiles as a banner is raised in her honor before an NCAA college basketball game against Notre Dame in Knoxville, Tenn. Tennessee seniors Cierra Burdick and Ariel Massengale were part of the last class of Lady Vols to play for Pat Summitt. (AP Photo/Wade Payne, File)
Glenn Campbell performs during The Goodbye Tour at the Ryman Auditorium on January 3, 2012 in Nashville, Tennessee. (Photo by Ed Rode/Getty Images)
Picture dated 18 May 1991 of US actor Charles Bronson during the 44th Cannes film festival, southern France. Bronson died 30 August 2003 in Los Angeles of complications from pneumonia. (Photo by Gerard Julien, AFP/Getty Images)
American painter Norman Rockwell, 75, poses in his Stockbridge, Mass., studio on Feb. 12, 1977. (AP Photo)
Boxer Sugar Ray Robinson in posed action, May 8, 1947. (AP Photo)
Abigail Van Buren, the 71-year-old advice columnist, was in Seattle to address the fall meeting of the Pacific Northwest Newspaper Association, Sept. 28, 1989. (AP Photo/Robert Kaiser)
Actor Peter Falk on March 10, 1989 at his home in Los Angeles. (AP Photo/Nick Ut)
Undated file photo of American actress and film star Rita Hayworth.(AP Photo)
392653 01: Actor Burgess Meredith performs in the television show 'The Twilight Zone.' (Photo Courtesy of Sci Fi Channel/Getty Images)
Actress Estelle Getty of "The Golden Girls" is shown at Trumps Restaurant in West Hollywood Jan. 29, 1986. (AP Photo/Steve Dakes)
LOS ANGELES - AUGUST 31: Actor James Doohan recieves his star on the Hollywood Walk of Fame August 31, 2004 in Los Angeles, California. (Photo by Mark Mainz/Getty Images)
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NOW WATCH: This incredible animation breaks down how Alzheimer's affects the brain over time

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