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 analyzed genetic data from nearly 450,000 people and identified 42 DNA regions associated with Alzheimer’s risk among APOE4 carriers, including 29 not previously reported in this analysis. The results point to genes active in oligodendrocytes as possible protective mechanisms, but they need further validation and may not apply across ancestry groups.
Researchers analyzing genetic data from nearly 450,000 people identified 42 DNA regions associated with Alzheimer’s risk among people carrying APOE4, the strongest common genetic risk factor for the disease. The findings, published in Alzheimer’s & Dementia, suggest that genes active in oligodendrocytes may help explain why some APOE4 carriers do not develop Alzheimer’s, but the possible protective effects are not yet established as treatments.
The study, led by Michael Belloy, an assistant professor at Washington University in St. Louis, focused on genetic variants that could modify risk in people with one or two copies of APOE4. The researchers reported 42 DNA regions linked to APOE4-related Alzheimer’s risk: 13 that had been identified previously and 29 newly identified in this analysis. The report does not establish that every region directly protects carriers; the signals require further testing.
The team also examined gene activity in post-mortem brain tissue from 424 donors. Many of the genes flagged in the analysis were active in oligodendrocytes, cells that form insulating sheaths around neurons and help them transmit electrical signals. Belloy highlighted TNS3 and CISD1 as possible risk modifiers: TNS3 is involved in oligodendrocyte maturation and survival, while CISD1 is important to their metabolism.
Another result involved MAPT, the gene that encodes tau. Higher MAPT activity appeared potentially protective in the analysis, a finding that Alzheimer’s Drug Discovery Foundation chief scientific officer Laura Nisenbaum described as intriguing to Being Patient. The report notes a possible connection to diranersen, a gene-silencing therapy aimed at lowering tau that is heading toward Phase 3 trials. The study itself did not test the therapy or show that its results predict how patients will respond.
Oligodendrocytes Offer a Research Lead
APOE4 raises the odds of Alzheimer’s but does not determine an individual’s outcome. Being Patient’s report says that about 60 percent of people with two APOE4 copies develop Alzheimer’s over their lifetime, meaning many do not. Finding genetic differences among carriers could help researchers understand which biological processes influence that variation and identify possible targets for future therapies.
The oligodendrocyte signal gives researchers a direction to investigate beyond the disease processes most often emphasized in Alzheimer’s research. If these cells contribute to protection, therapies that affect their function could eventually be studied as a way to modify risk. That remains a research possibility, not a clinical recommendation: no FDA-approved drugs target TNS3 or CISD1 for Alzheimer’s, and the study did not show that increasing their activity would prevent disease.
The findings may also help explain why genetic risk alone cannot predict an individual’s future with certainty. As Nisenbaum told Being Patient, “APOE4 is the strongest common genetic risk factor for Alzheimer’s but it doesn’t act alone.” The reported variants could be part of that broader picture, although their individual effects and practical use are still unknown.
genetic testing kits for Alzheimer's risk
As an affiliate, we earn on qualifying purchases.
As an affiliate, we earn on qualifying purchases.
How Researchers Searched for Protection
Rather than treating APOE4 as a guarantee of disease, the researchers looked for genetic signals that might alter its association with Alzheimer’s. That approach compares genetic patterns among people at elevated risk and can suggest why risk varies. The study’s findings add to earlier research into protective variants, including the Christchurch variant, which has been studied in people with inherited forms of Alzheimer’s.
The report describes a Colombian woman with a genetic form of Alzheimer’s who remained cognitively healthy until her 70s and carried two copies of the Christchurch variant. That case prompted interest in whether one copy might also confer protection; the source notes that a more recent investigation raised doubts about the reliability of some studies on the variant. The current research concerns a different set of signals and should not be taken as confirmation of the Christchurch findings.
Genetic research is increasingly informing drug-development efforts, including gene-silencing approaches and other tools that can alter gene activity. In this study, however, the evidence comes from statistical genetic associations and post-mortem brain tissue, not from a clinical trial testing a treatment based on the identified genes.
““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
Key Limits of the Genetic Evidence
The study identifies associations, not proof that particular genes shield APOE4 carriers from Alzheimer’s. The researchers’ signals still need independent validation and experimental testing to determine whether the genes affect disease biology, how large any effects are, and whether changing their activity could be safe or useful.
The sample also limits how broadly the findings can be applied. Most participants were of European ancestry, so it is not clear whether the same variants or effects are present in other populations. In addition, only 40 percent of the participants whose genetic data were analyzed had biomarker confirmation of Alzheimer’s, according to the report; some clinical diagnoses may have been incorrect.
The post-mortem gene-activity analysis used tissue from people who had died, including donors who may have been in later stages of disease. Nisenbaum cautioned that such samples may not represent earlier disease stages. The report does not provide a timetable for validation studies, nor does it show that a gene-targeting medicine can reduce an APOE4 carrier’s risk.
Validation Before Treatment Claims
Belloy said further experimental and validation studies are needed. Researchers will need to check whether the genetic signals recur in other groups, clarify how the candidate genes act in brain cells, and test whether the findings hold across people with different ancestries and disease stages.
For now, the results offer research leads rather than a change in Alzheimer’s care. TNS3 and CISD1 have no FDA-approved Alzheimer’s medicines targeting them, and the MAPT observation does not establish that diranersen or another tau-directed treatment will benefit APOE4 carriers. The next meaningful developments will be independent confirmation and laboratory or clinical research that directly tests the proposed mechanisms.
Key Questions
What did the study find about APOE4 and Alzheimer’s?
Researchers reported 42 DNA regions associated with Alzheimer’s risk among APOE4 carriers, including 29 newly identified in their analysis. The results suggest that some genetic factors may modify risk, but they do not prove that each region is protective.
Which genes were highlighted as possible protective factors?
The report highlights TNS3 and CISD1 as candidate risk modifiers linked to oligodendrocyte function. It also describes a potentially protective association involving higher MAPT activity. These findings need further validation.
Does carrying APOE4 mean someone will develop Alzheimer’s?
No. APOE4 increases risk but does not determine an individual’s outcome. The source report says about 60 percent of people with two copies develop Alzheimer’s over their lifetime; that figure does not mean every carrier will develop the disease.
Can these findings guide treatment now?
No treatment recommendation follows from this study. The research did not test a therapy, and the report says there are no FDA-approved Alzheimer’s medicines targeting TNS3 or CISD1. The candidate signals require additional research.
Do the findings apply to all ancestry groups?
That is not yet known. Most study participants were of European ancestry, so researchers need to assess whether the results generalize to other populations.
Source: rss
Fall Picks
fall essentials
As an affiliate, we earn on qualifying purchases.
