Researchers have made a significant discovery by removing the APOE ε4 gene from neurons in mice, resulting in a remarkable reduction in Alzheimer’s disease characteristics, such as cell death and the proliferation of tau tangles. This groundbreaking finding indicates that the APOE ε4 gene plays a crucial role in promoting the development of Alzheimer’s and unveils potential therapeutic targets for treating the disease. Credit: NIA
A recent study, supported by the National Institute on Aging (NIA), has revealed a novel therapeutic approach for treating Alzheimer’s disease by eliminating a genetic risk factor in neurons.
The study, published in Nature Aging, demonstrates that removing a specific genetic variant can mitigate the pathological features of Alzheimer’s disease in mice. The research suggests that the activity of the APOE ε4 gene within neurons contributes to the progression of Alzheimer’s.
Certain genetic factors, including the apolipoprotein E (APOE) gene, have been associated with an increased likelihood of developing dementia, specifically Alzheimer’s disease. The APOE gene exists in different forms known as alleles.
Among these alleles, the APOE ε4 allele is recognized as the most potent genetic risk factor for Alzheimer’s. However, the exact mechanism by which it raises the risk of the disease remains poorly understood. Some studies propose that the activity of APOE ε4 in astrocytes, a type of glial cell, is detrimental to the brain.
To shed light on this issue, a team of researchers from the Gladstone Institutes investigated the APOE ε4 gene’s activity within neurons, which are responsible for transmitting signals throughout the nervous system. Using genetic engineering techniques, the scientists successfully removed the APOE ε4 gene from neurons in mice that already carried a variant of tau, a protein known to form damaging tangles in the brains of individuals with Alzheimer’s.
The removal of the APOE ε4 gene from neurons significantly reversed the typical brain damage observed in mice with the tau variant. Notably, this intervention reduced cell death and the propagation of tangles in the hippocampus, a brain region frequently affected by Alzheimer’s. Moreover, the loss of myelin, the protective insulation around nerves facilitating signal transmission, which occurs in Alzheimer’s, was alleviated by removing neuronal APOE ε4. This intervention increased the presence of protective myelinating cells to levels comparable to those seen in healthy mice.
Furthermore, eliminating neuronal APOE ε4 gene expression reduced the occurrence of “reactive” glial cells to levels observed in control mice. In a healthy brain, glial cells support neurons, but in Alzheimer’s, they can become unhealthy and reactive, contributing to neurodegeneration.
The researchers also noted a similar positive shift in the genetic activity of disease-associated brain cell populations upon removing the APOE ε4 gene in neurons. This shift transformed several types of brain cells from a damaging state to a protective one.
These findings provide valuable insights into potential therapeutic targets for Alzheimer’s disease associated with APOE ε4 and enhance our understanding of how this gene is implicated in various disease characteristics. Further research is necessary to fully comprehend the role of APOE ε4 in Alzheimer’s.
Reference: “Neuronal APOE4 removal protects against tau-mediated gliosis, neurodegeneration, and myelin deficits” by Nicole Koutsodendris, Jessica Blumenfeld, Ayushi Agrawal, Michela Traglia, Brian Grone, Misha Zilberter, Oscar Yip, Antara Rao, Maxine R. Nelson, Yanxia Hao, Reuben Thomas, Seo Yeon Yoon, Patrick Arriola, and Yadong Huang, 20 February 2023, Nature Aging.
DOI: 10.1038/s43587-023-00368-3
The study received funding from the National Institute on Aging.
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Frequently Asked Questions (FAQs) about Alzheimer’s disease
What did the researchers discover about the APOE ε4 gene in relation to Alzheimer’s disease?
The researchers discovered that removing the APOE ε4 gene from neurons in mice resulted in a significant decrease in Alzheimer’s disease hallmarks, such as cell death and tau tangle proliferation. This suggests that the APOE ε4 gene plays a significant role in promoting Alzheimer’s development.
What is the significance of removing the APOE ε4 gene from neurons?
Removing the APOE ε4 gene from neurons in mice showed promising results in reducing the damage typically observed in the brains of mice with Alzheimer’s disease. It led to a decrease in cell death, the spread of tangles, and the appearance of reactive glial cells. These findings offer new insights into potential therapeutic targets for Alzheimer’s disease.
How does the APOE ε4 gene contribute to Alzheimer’s disease?
While the exact mechanism is not well understood, studies suggest that the activity of the APOE ε4 gene, particularly in astrocytes, may harm the brain. This gene variant is recognized as the strongest genetic risk factor for Alzheimer’s disease.
What are the implications of the study’s findings?
The study’s findings provide a better understanding of the role of the APOE ε4 gene in Alzheimer’s disease. It highlights the involvement of this gene variant in various disease characteristics and offers potential therapeutic targets for treating Alzheimer’s related to APOE ε4.
What future research is needed in this area?
Further research is necessary to fully comprehend the specific mechanisms by which the APOE ε4 gene influences Alzheimer’s disease. Additionally, more studies are needed to explore and develop targeted therapeutic interventions that can mitigate the effects of this genetic risk factor in Alzheimer’s patients.
More about Alzheimer’s disease
- NIA (National Institute on Aging): Link to NIA
- Nature Aging: Link to Nature Aging
- “Neuronal APOE4 removal protects against tau-mediated gliosis, neurodegeneration and myelin deficits” (Study): Link to Study
