How diagnosing Alzheimer’s and other dementias is changing
An international coalition of brain researchers is suggesting a new way of exploring, diagnosing and treating Alzheimer's.1 Instead of defining the disease through symptoms such as memory loss or fuzzy thinking, scientists are now focusing on the biological changes in the brain associated with Alzheimer's. These include the plaques and tangles that build up in the brains of people with the disease; they are the prime suspects in cell death and tissue loss which causes Alzheimer’s.
How Alzheimer’s is Currently Diagnosed
Currently, a certain set of signs and symptoms in an individual typically trigger testing and treatment for Alzheimer’s. But researchers are beginning to see flaws in this approach. When examining the brains of people receiving experimental drugs for the disease, about 30% of the people who met all the appropriate clinical criteria did not have Alzheimer's disease. Their memory or thinking problems were being caused by something else.
This has prompted researchers to look for more reliable ways of determining whether someone really has Alzheimer's versus another form of dementia or some other ailment which may be causing Alzheimer-like symptoms. These researchers are focused on the two best-known brain changes associated with the disease. Without getting too technical, these brain changes involve amyloid and tau-related neurodegeneration; plaques and tangles.
"What we're seeing now is that Alzheimer's disease is defined by the presence of plaques and tangles in your brain," said Clifford Jack, an Alzheimer's researcher at Mayo Clinic Rochester. Jack, who is also an author of the central paper describing the proposed new research framework, noted that “symptoms become the result of the disease, not the definition of the disease."
A New Way to Diagnose Alzheimer’s
Instead of using the early signs of Alzheimer’s as the indicators for diagnosis, neuroscientists are now thinking that research should focus on biological brain changes, including these damaging plaques and tangles, and what can be done to prevent and/or treat these conditions before they begin to manifest as the symptoms of Alzheimer’s.
Plaques are abnormal clusters of chemically “sticky” proteins called beta-amyloid that build up between nerve cells. The small clumps may block cell-to-cell signaling at synapses. They may also activate immune system cells that trigger inflammation and devour disabled cells.2
Tangles form inside dying cells and are twisted fibers of a protein called tau. In healthy areas, tau helps keep the transport system on track. But in areas where tangles are forming, the twisted strands of tau essentially disintegrate the transport system so that nutrients and other essential supplies can no longer move through the cells, which eventually die.2 Though most people develop some plaques and tangles as they age, those with Alzheimer’s tend to develop far more.
In the past, it was virtually impossible to detect plaques and tangles in a living person. But over time, scientists have developed a number of ways to spot the abnormalities using special brain scans or tests of spinal fluid. These tests for what are known as ‘biomarkers of Alzheimer's” are allowing scientists to do experiments that would have been impossible relying on symptoms alone. This testing bodes well for starting preventative treatment years before the onset of Alzheimer’s symptoms.
Elizer Masliah, who directs the Division of Neuroscience at the National Institute on Aging, has said that there is a stage of the disease where there are no symptoms, but where these biomarkers do manifest themselves.1 Testing for these biomarkers would allow for an entirely new approach to looking at Alzheimer’s and treating it.
At this point, the new biological approach to defining and better treating Alzheimer’s is intended only for research studies. "It's a research framework meant to be tested, a tool for researchers, not for the doctor's office," says Maria Carrillo, chief scientific officer of the Alzheimer's Association.1 If it is eventually adopted however, it would help researchers study patients whose brain function is still normal but who are likely to develop dementia caused by Alzheimer's.
Biomarkers are still in an early stage of development and may not yet be a reliable replacement for clinical symptoms in research but they offer hope that when drugs become available to prevent Alzheimer’s, biomarker tests can better determine who should get these drugs and improve early Alzheimer’s diagnosis.
The proposal, and more commentary on it may be found in the April 2018 issue of Alzheimer's & Dementia: The Journal of the Alzheimer's Association.
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