Using an animal model, the researchers will employ a tracer for positron emission tomography (PET scanning) to image microtubules – microscopic tubes that help define the structure and movement of cells – in the brain.
“Microtubules are message carriers within neurons that are very tightly bundled in a healthy brain,” said the project’s lead investigator, Kiran Solingapuram Sai, Ph.D., assistant professor of radiology at Wake Forest School of Medicine, part of Wake Forest Baptist Health. “If microtubules start disintegrating or detangling, they can’t do their job anymore. The neurons begin to degenerate and cognition declines.”
While microtubule impairments are implicated in several stages of the progression of Alzheimer’s, Sai said he believes that the related neurodegeneration occurs significantly before the appearance of any symptoms of the disease. He and his team hope to show that determining the condition of neural microtubules can be used to predict the onset of Alzheimer’s sooner than is now possible.
For the study the researchers will inject the microtubule PET tracer in healthy and Alzheimer’s mice and scan their brains at two-month intervals. The imaging tracer, developed by Sai’s lab in collaboration with scientists at Columbia University and the first of its kind capable of penetrating the brain, are hypothesized to bind only to those microtubules that are intact. The tracer’s lack of binding, conversely, should indicate that the microtubules have deteriorated and the onset of disease has begun.
When that happens, the investigators will relate the PET imaging data to the subject’s cognition, behavior and accumulation of the proteins tau and beta- amyloid that are involved with Alzheimer’s to determine if the condition of the microtubules is in fact a biomarker for neural degeneration and cognitive impairment.
“This approach could significantly improve both imaging strategies to track Alzheimer’s in its initial stages and our ability to more precisely treat patients with neurodegenerative diseases early on,” Sai said.
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