A distinguished group of researchers wants to redefine Alzheimer’s disease by focusing on biomarkers instead of symptoms, such as memory loss.
For a better understanding of what’s being proposed, WUWF called on Dr. Rodney Guttmann, a professor in the University of West Florida Department of Biology, who is now leading clinical trials at the university focused on agitation in Alzheimer’s disease.
The proposal from the National Institute on Aging and Alzheimer’s Association is part of an effort to update guidelines approved in 2011, and Guttmann believes it represents an important shift in how Alzheimer’s disease is going to be viewed – particularly from a research perspective.
“They really want to focus on biomarkers, trying to improve the research direction to target plaques and tangles, which are the original definition of Alzheimer’s disease back in the early 1900’s,” said Guttmann, clarifying that the clinical definition will remain unchanged. “So, this is a reflection of kind of the reality on the ground that Alzheimer’s is a disease of plaques and tangles in the brain.”
According to Dr. Guttmann, those pathological changes in the brain result in the cognitive decline that’s observed in a clinical setting. And, in the past two to three decades, it’s been the changes in brain function that’s been driving how Alzheimer’s is defined.
For researchers, the proposed change means a shift from focusing on first on brain function, such as memory loss and other symptoms, and instead beginning with biological changes in the brain associated with Alzheimer’s disease. The primary reason is because scientists have found that those changes within the brain, the formation of plaques and tangles, actually starts happening decades – 30 to 40 years - before the clinical symptoms occur.
Dr. Guttmann adds that the most recent clinical trials that have focused on the plaque-busting drugs, don’t seem to be having an effect on cognition.
“So, I think that’s what’s driving this notion that we need to go back and look at the foundational element of Alzheimer’s disease, plaque and tangle formation; what is driving that, how can we detect that, and how can we change that path, with a goal of treating that cognitive decline that happens later.”
In a closer examination of plaques and tangles, while everyone forms them, they are abnormal protein deposits that occur in the brain of people with Alzheimer’s disease.
A significant factor in the proposal to define Alzheimer’s based on biomarkers is that doctors now have the tools to definitively diagnose the disease before a person dies.
“Many people have heard and I hear it at many presentations I give, “Oh, I thought you could only diagnose Alzheimer’s disease upon death,” said Guttmann. “That has been the case traditionally that Alzheimer’s is defined by plaques and tangles, and now we can image those things in living time, in living people.”
Dr. Guttman says this newly proposed research framework is very much in line with how he views Alzheimer’s disease and the biomarkers research he’s been conducting for several years at UWF.
“Biomarkers are (going to) be key,” said Guttmann, noting that everything on the market now treats symptoms or changes in cognition and behavior. He says the biomarkers, now identified through cerebrospinal fluid (CSF) and blood testing, would be useful for an earlier diagnosis when there are no symptoms.
“It is well known in the literature that people with Alzheimer’s disease have changes in their brain occurring in their thirties, forties, and fifties, so 20-40 years before clinical symptoms occur. So, it makes logical sense that we want to be able to detect that as early as possible and there’s (currently) no way to do that in a clinical setting.”
Biomarkers, he says, are the future in terms of developing reliable ways to screen for Alzheimer’s disease, similar to the testing that’s now available for other diseases such as diabetes. Additionally, they can be used in establishing what’s called ‘disease modifying therapy,’ which currently doesn’t exist.
Clearly, Dr. Guttmann is optimistic about this new vision for Alzheimer's researchers who are working to develop strategies for the prevention, treatment and eventual cure of the disease.
More details about the new research framework are available in the April 2018 issue of Alzheimer’s & Dementia: The Journal of the Alzheimer’s Association. The first author is Clifford R. Jack, Jr., M.D., of Mayo Clinic Rochester, MN.
UWF is currently conducting clinical trials on agitation in Alzheimer’s. More information, 850-474-3181 or ClinicalTrials@uwf.edu.