3 Alzheimer's biomarkers build over time but decline after symptoms appear

Certain biomarkers that can point to the presence of Alzheimer's build and then peak in the body over a period of years, then drop after symptoms appear, researchers have determined. Why this happens is unclear. But the discovery could redefine how drug developers approach the measurement and testing of new treatments to combat the disease.

A team at Washington University School of Medicine made the discovery, and Science Translational Medicine published their findings on Mar. 5. The National Institutes of Health and the National Institute on Aging are among the study sponsors.

For their work, the research team (led by neurology professor Anne Fagan) looked at data from 26 patients who participated in the Dominantly Inherited Alzheimer Network (DIAN) project at Washington University in St. Louis. All carried gene mutations that can cause rare, inherited forms of the disease, according to the university.

In this patient pool, the scientists studied the biomarkers tau, p-tau and VILIP-1 over time. Each are crucial in Alzheimer's studies because they generally increase in the body following neuronal injury. Researchers believe they're linked to cognitive decline, and the advance of Alzheimer's appears to make dying brain cells release the biomarkers into the body, after which they make their way into spinal fluid. They found that each biomarker increased in number over time in patients who had not yet developed dementia. But for patients who developed dementia, the three biomarkers declined in the body gradually at small but consistent rates.

Right now, there is speculation about what the results mean, but knowing that the biomarkers decline in number once dementia hits patients changes things. Ideally, researchers now want to combat Alzheimer's before it leads to too much neurological decline, and so drug developers are looking to hit the disease even before symptoms appear and its advance causes cell damage. But different levels of these biomarkers will help determine whether new drugs are working or not. So it will likely be crucial to understand why the biomarkers increase and then decline once Alzheimer's symptoms appear.

"Changes in the levels of these biomarkers likely will be among the criteria we use to assess the success or failure of Alzheimer's drugs," Fagan said in a statement, "so we need to know how these biomarkers normally behave in the absence of treatment."

In other words, much more work is needed before this promising finding can be placed in proper context and help inform what has so far been a discouraging quest for viable Alzheimer's treatments. The research team promises more work and said they're compiling more data on DIAN participants. They're also continuing to follow patients who took part in their study and planning new work to determine whether biomarker levels also change in patients with more common forms of Alzheimer's, which isn't typically diagnosed until later in life.

- read the release
- here's the journal abstract

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