Plaque buildup trajectory may serve as a clue for Alzheimer's

University of Pennsylvania researchers and others believe that earlier prediction of Alzheimer's disease may be possible by measuring amyloid plaque progression and patterning in the brain over time, rather than the end result. If their work is successful, it could serve as a viable way to diagnose Alzheimer's or cognitive decline sooner and create a new avenue through which to test promising treatments.

Their research, detailed in the Journal of Neurobiology of Aging, establishes a possible new biomarker by redefining how clinicians look at an old one. For some time now, scientists have relied on total amyloid plaque deposits in the brain as a clue to help diagnose Alzheimer's or other forms of cognitive decline. But the discovery by the team from Penn Medicine's Department of Radiology, along with researchers from Johns Hopkins and the National Institute on Aging, potentially upends that measurement by adding a new, more nuanced process for biomarker screening.

"It appears to be more about the spatial pattern of this plaque progression, and not so much about the total amount found in brains," Christopher Davatzikos, the paper's senior author and a professor at the University of Pennsylvania's Perelman School of Medicine, said in a statement. "This is important because it potentially answers questions about the variability seen in clinical research among patients presenting plaque. It accumulates in different special patterns for different patients, and it's that pattern growth that may determine whether your memory declines."

Their work involved 64 patients from the NIA's Baltimore Longitudinal Study of Aging (BLSA), with an average age of about 76. Specifically, the team used patients' PET brain scans, which captured amyloid changes thanks to a radiotracer known as Pittsburgh compound B (PiB). This enabled them to measure amyloid plaque density and volume and its spatial distribution within the brain, crucial data to help build detailed images. Next, the team broke the group into two segments: "most stable" and "most declining."

The scientists found the brain scans didn't have much difference in the total amount of amyloid plaque. But the spatial patterns showed a big contrast. In the "stable" group, there was relatively early buildup in the frontal lobes. The "declining" subset, however, reflected buildup in the temporal lobes. The discovery reflects the nuance with which amyloid buildup progression can indicate cognitive decline. As the researchers note, their work indicated that amyloid buildup can hit the brain's function depending on its trajectory, which in turn impacts cognitive impairment in different ways.

More work must be done, though, to define how amyloid trajectory can serve as a viable biomarker for Alzheimer's and other cognitive decline. The researchers said they hope to study more people who have mild cognitive impairment. They also plan to pursue additional follow-up scans of patients from the BLSA study. The long-term goal is to fine-tune the process of using amyloid imaging as a biomarker for research and the clinic. They'll also continue their attempt to fully decipher the link between the location of amyloid plaque and cognitive decline.

- read the journal abstract
- here's the release

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