“If you look across cell culture samples from 50 people, you can predict from the Aβ and tau profiles some features of the cognitive status of that person – their rate of cognitive decline and whether they developed AD – which is absolutely remarkable,” Young-Pearse said. The researchers measured Aβ and tau generated by the stem cell-derived neurons and found that specific Aβ and tau species were associated with the levels of plaque and tangle deposition in the brain and the trajectory of cognitive decline. After death, the brains of the deceased also were studied and compared to their cultured brain cells in a dish. While the subjects were alive, detailed clinical records and full genome sequencing were collected for each person. Stem cell lines were generated from blood samples of over 50 of these individuals, who lived to an average of 90 years of age. All individuals entered the ROS and MAP studies with no history of AD or any other neurological diagnosis, but more than one-third went on to develop AD over time. The study leveraged a large cross-institutional collaborative effort that follows a cohort of people from the Religious Orders Study (ROS) and the Rush Memory and Aging Project (MAP) at Rush University. This large set of human cell lines from AD and aged normal people provide the scientific community with a powerful experimental system for untangling why some people develop AD and others do not.” “Those stem cell-derived neuronal profiles have a predictive nature, in terms of the clinical outcome of an individual’s Alzheimer’s disease. “We are finding that different genetic backgrounds in humans generate different profiles of Aβ and tau,” said Young-Pearse, an associate professor in the Ann Romney Center for Neurologic Diseases at Brigham and co-leader of the HSCI Nervous System Diseases Program. Specific forms of amyloid beta-protein (Aβ) and tau protein associated with cognitive decline and AD were identified, which reveal signaling pathways influencing the production of these toxic species. The power of this new resource was demonstrated through a series of studies that turned these stem cells into brain cells and then analyzed molecular pathways active in these living neurons in a dish. In their study, published in Neuron, the team generated induced pluripotent stem cell (iPSC) lines from over 50 individual subjects for whom longitudinal clinical data, quantitative neuropathology data, and rich genetic and molecular profiling of brain tissue were also available. Researchers from Brigham and Women’s Hospital, led by Harvard Stem Cell Institute (HSCI) Principal Faculty Tracy Young-Pearse, Ph.D., have developed a method to examine living brain cells and predict the rate of cognitive decline in humans. IPSC-derived neurons derived from human participants in the Religious Order Study and Memory and Aging Project.Ī new brain model has been developed that will allow patient-specific insights in Alzheimer’s disease (AD).
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