Science

Does ApoE in Neurons Drive Selective Vulnerability in Alzheimer’s?

From the Alz Forum

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Scientists know that neurons can generate a dribble of ApoE, but it is considered a drop in the bucket relative to the massive amounts of it churned out by their glial neighbors. Nevertheless, a study published May 6 in Nature Neuroscience makes the case that neuronal ApoE not only signals distress, but also may have a hand in killing the neurons. Using single-cell transcriptomics, researchers led by Yadong Huang at the University of California, San Francisco, report that, in mice, certain neurons ratchet up ApoE expression as the animals age. They do so earlier, and with more gusto, in mice expressing ApoE4. Similarly, in people, particular neurons rev up ApoE in the early stages of Alzheimer’s disease. In later stages, those neurons were more likely to have perished, hinting that stepped-up ApoE expression could spell doom for neurons. Those same neurons also start expressing immune-response genes such as that for the antigen-presenting, major histocompatibility complex I. The researchers tied MHC-I to tau pathology within individual neurons.

  • In mice, neurons that express ApoE also express antigen-presenting genes.
  • This rises with age and, in ApoE4 knock-ins, starts earlier.
  • Deleting ApoE from neurons wards off age-related death.
  • In AD, neuronal ApoE tracks with progression, perhaps with cell loss.

“This fascinating paper describes a novel role for neuronal ApoE expression in Alzheimer’s disease,” wrote Gwyneth Welch and Li-Huei Tsai of the Massachusetts Institute of Technology


Read the full article on the Alz Forum Website – https://www.alzforum.org/news/research-news/does-apoe-neurons-drive-selective-vulnerability-alzheimers

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