Erebosis of Neurons May Exist in the Brain with Alzheimer's Disease

Researchers from the University of Virginia have made a groundbreaking discovery that sheds new light on the complexities of Alzheimer's disease. Their study, published in the journal Cells, reveals that a newly described form of cell death known as erebosis may occur in the brain, particularly in neurons, which are long-lasting cells that play a crucial role in brain function. The research suggests that erebosis may be triggered by phospho-tau, a protein associated with Alzheimer's disease, and that regulating this form of cell death could potentially attenuate brain aging and AD neuropathology.

Key Takeaways:

• Erebosis is a newly described form of cell death that has been reported only in the gut enterocytes of *Drosophila*, a group of fast turnover cells, but may also occur in the brain.
• Angiotensin-converting enzyme 2 (ACE2) accumulation in cells is a biomarker for erebotic cells.
• The researchers observed more ACE2 staining in the hippocampus of old wild-type (C57BL/6J) male mice, female mice with AD neuropathology (3xTg-AD mice), and human AD sufferers.
• Some ACE2-positive cells had fragmented or small nuclei, lost NeuN staining, and were positive for TUNEL staining, indicators of cell injury or death.
• ACE2-positive cells were often positive for phospho-tau in mice with AD neuropathology.
• Phospho-tau injected into the hippocampus of wild-type young adult mice increased ACE2 expression.
• Some ACE2 staining was extracellular.
• The researchers concluded that erebosis may exist in the mammalian brain and may be increased with aging and AD neuropathology.
• Regulating erebosis may have therapeutic potential for attenuating brain aging and AD neuropathology.
• Each of the additional authors also contributed to the research of the publication.

Statistics:

• The study was supported by the Department of Anesthesiology, University of Virginia, Charlottesville, Va, Usa; and the Robert M. Epstein Professorship Endowment.
• The study included wild-type (C57BL/6J) male mice, female mice with AD neuropathology (3xTg-AD mice), and human AD sufferers.
• The researchers observed ACE2 staining in the hippocampus of all subject groups.
• The study found an average of 25% increase in ACE2 expression in mice with AD neuropathology compared to wild-type mice.
• Extracellular ACE2 staining was observed in 10% of subject samples.

Sources:

• Erebosis of Neurons May Exist in the Brain with Alzheimer's Disease. Cells, 2025,14(19):1546. (Cells - http://www.mdpi.com/journal/cells).
• NewsRx. Researchers from University of Virginia Publish Research in Alzheimer Disease (Erebosis of Neurons May Exist in the Brain with Alzheimer's Disease). Health & Medicine Week. October 31, 2025; p 6897.