TL;DR
Get comfort and care essentials delivered free — and shop member deals
- Fast, free delivery on millions of items
- Access to Prime Big Deal Days deals on October 6–7
- Prime Video, Amazon Music and more included
Researchers analyzing genetic data from nearly 450,000 people identified 42 DNA regions associated with Alzheimer’s risk among people carrying APOE4, including 29 regions not previously reported. The findings point to possible protective effects involving oligodendrocytes, but they do not establish that any gene prevents Alzheimer’s or provide a proven treatment.
Researchers analyzing genetic data from nearly 450,000 people identified DNA regions that may help explain why some carriers of the APOE4 Alzheimer’s risk variant do not develop the disease. The study, published in Alzheimer’s & Dementia, points to possible roles for oligodendrocytes, brain cells that support communication between neurons, but its findings are not proof that the identified genes prevent Alzheimer’s or can yet be used as treatments.
Michael Belloy, an assistant professor at Washington University in St. Louis, and colleagues focused on people carrying one or two copies of APOE4 who had not developed Alzheimer’s. The source report says APOE4 can raise Alzheimer’s risk by about four to 12 times; the level of risk varies, and carrying the variant does not mean a person will inevitably develop the disease.
The team identified 42 DNA regions associated with APOE4 status: 13 that had been reported previously and 29 described as new in this study. The researchers also examined gene activity in post-mortem brain tissue from 424 donors, looking at whether candidate genes were more active in particular cell types.
Several candidate genes were active in oligodendrocytes, which form protective, fatty coverings around nerve fibers and help electrical signals travel efficiently. The report highlights TNS3, which is involved in oligodendrocyte maturation and survival, and CISD1, which is involved in the cells’ metabolism. The analysis suggests these genes may modify risk; it does not establish that changing their activity would prevent disease.
Possible Protective Pathways in the Brain
The findings may help researchers investigate why APOE4 does not lead to the same outcome for every carrier. Although APOE4 is a major common genetic risk factor, other genetic and biological factors may influence an individual’s risk. Identifying those factors could point scientists toward mechanisms that make the brain more resilient or alter disease processes.
The proposed role for oligodendrocytes is relevant because much Alzheimer’s research has focused on other processes, including amyloid and tau. If future studies confirm that oligodendrocyte-related genes affect risk, those cells could become another avenue for research and drug development. That possibility is still preliminary: association in genetic and post-mortem data does not show that a drug aimed at these genes would be safe or effective.
The researchers described TNS3 and CISD1 as potential candidates for further investigation. The source report says there are currently no FDA-approved medicines targeting them that could be repurposed for Alzheimer’s. Any treatment based on these findings would require additional research and clinical testing.
brain health supplements for memory
As an affiliate, we earn on qualifying purchases.
As an affiliate, we earn on qualifying purchases.
How APOE4 Fits the Findings
APOE4 is the strongest common genetic risk factor for Alzheimer’s, but it is not a diagnosis or a guarantee of disease. Laura Nisenbaum, chief scientific officer of the Alzheimer’s Drug Discovery Foundation and not involved in the study, told Being Patient that APOE4 does not act alone. The report notes that even among people with two copies, lifetime risk is not certain: it cites an estimate that about 60 percent of people with two copies develop Alzheimer’s.
The study also examined MAPT, the gene that encodes tau. Nisenbaum said the finding that higher MAPT activity might be protective was intriguing, given tau’s role in Alzheimer’s tangles. She noted that the post-mortem samples came from people who died in later stages of disease, however, so gene activity in those brains may not represent earlier disease stages. The report mentions diranersen, a tau-lowering gene-silencing therapy from Biogen that was heading toward Phase 3 trials, as a possible point of relevance—not as a treatment validated by this study.
Researchers have previously investigated other examples of apparent genetic protection, including the Christchurch variant in a person with an inherited form of Alzheimer’s. Those cases are a separate line of research and do not confirm the effects of the genes identified here.
“Ultimately, we found a set of genes that look promising to counter Alzheimer’s disease risk due to APOE4.”
— Michael Belloy, assistant professor at Washington University in St. Louis, speaking to Being Patient
oligodendrocyte support supplements
As an affiliate, we earn on qualifying purchases.
As an affiliate, we earn on qualifying purchases.
Limits on the Genetic Evidence
The results are associations that require independent validation. The source report says most participants were of European ancestry, so it remains unclear whether the findings apply to people from other ancestry groups. The study’s genetic data also relied on clinical diagnoses, and only about 40 percent of those individuals had biomarker confirmation; some diagnoses may therefore have been incorrect.
The post-mortem gene-activity analysis involved 424 donors and captured tissue after death, often after disease had advanced. It cannot by itself show whether gene activity changed before Alzheimer’s began, resulted from the disease, or influenced the course of illness. The report also does not provide effect sizes for each candidate that would establish how much any one region changes risk.
Researchers have not shown that activating TNS3 or CISD1 prevents Alzheimer’s, nor that the genes can be safely targeted in people. The study does not provide a new screening test, individual risk estimate, or clinical recommendation. Whether the findings translate into prevention or treatment remains unknown.
As an affiliate, we earn on qualifying purchases.
Validation Before Treatment Claims
Belloy said further validation and experimental studies are needed to test whether the identified genetic signals hold up and to clarify how they may affect Alzheimer’s risk. Follow-up work would also need to examine whether the results generalize across ancestry groups and whether the relevant biological activity occurs early enough in disease to be a useful target.
Researchers would need to test the proposed mechanisms in laboratory and other experimental systems before considering medicines aimed at them. If a candidate target proves relevant, development would still require studies of safety and effectiveness. For now, the next step is establishing whether these genetic associations reflect protective biology rather than patterns specific to the study’s participants or tissue samples.
genetic testing kits for Alzheimer's risk
As an affiliate, we earn on qualifying purchases.
As an affiliate, we earn on qualifying purchases.
Key Questions
Does carrying APOE4 mean someone will develop Alzheimer’s?
No. APOE4 raises risk but does not guarantee Alzheimer’s. The source report cites an estimate that about 60 percent of people with two copies develop the disease over their lifetime.
Which genes did the study identify as possible risk modifiers?
The report highlights TNS3 and CISD1 as candidate genes that may modify risk among APOE4 carriers. The study does not prove that either gene prevents Alzheimer’s.
How many genetic regions were associated with APOE4 status?
The researchers reported 42 DNA regions: 13 previously identified and 29 described as new. Their association with APOE4 status needs further validation.
Could the findings lead to an Alzheimer’s medicine?
Possibly, but that is not established. Researchers would first need to confirm the findings and test how the genes work. The source report says there are no FDA-approved medicines targeting TNS3 or CISD1 for Alzheimer’s.
Do the findings apply to all populations?
That is not yet clear. Most people in the study were of European ancestry, and additional research is needed to assess whether the results apply to other populations.
Source: rss
Halloween Picks
halloween
As an affiliate, we earn on qualifying purchases.
