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Study Probes Blood Biomarker for Early-stage Alzheimer's Disease

March 06, 2024

Recent research has uncovered a new blood biomarker for early-stage Alzheimer’s disease – the phosphorylation or modification of the tau protein at threonine 217 (pT217-tau).

However, it has largely remained a mystery as to how and when this biomarker emerges in the brain, because this marker rapidly degrades after death, usually before human brains can be studied.

Yale researchers in the departments of Psychiatry and of Neuroscience, in collaboration with research colleagues at Massachusetts General Hospital, sought to locate early-stage, soluble pT217-tau in the brains of very old monkeys with similar pathology to humans, where brains could be studied more quickly using powerful microscopes that provide very high resolution.

Their findings, published in Alzheimer’s & Dementia: The Journal of the Alzheimer’s Association, revealed pT217-tau in its earliest form in neurons in early stages of degeneration, as well as evidence of pT217-tau “seeding” between neurons.

"It was particularly exciting for us to visualize pT217-tau trafficking across excitatory synapses in the brain, where it becomes exposed to the extracellular space and can be captured in blood plasma, and thus can serve as a biomarker of ensuing Alzheimer's disease,” said lead author Dibyadeep Datta, PhD, assistant professor of psychiatry.

Identifying the earliest signs of disease may help to guide treatments that can prevent Alzheimer's disease in the future.

Funding was provided by the National Institutes of Health, the American Federation for Aging Research Faculty Transition Award, the Yale Alzheimer’s Disease Research Center, the Alzheimer’s Disease Research Unit, and the MacBrain Resource Center.

Submitted by Christopher Gardner on March 06, 2024