Scientists studied a specific gene called MTHFR that comes in different versions. Some versions of this gene may make it harder for your body to process certain B vitamins and break down a substance called homocysteine. When homocysteine builds up in your blood, it might increase your risk of developing Alzheimer’s disease. Researchers compared 120 people with Alzheimer’s to 120 healthy people and found that those with certain MTHFR gene versions were more likely to have Alzheimer’s, along with higher homocysteine levels and lower B vitamin levels. This discovery could help doctors identify who might be at higher risk and develop new ways to prevent or treat Alzheimer’s.

The Quick Take

  • What they studied: Whether certain variations in a gene called MTHFR increase the chances of developing Alzheimer’s disease and how this gene affects the body’s ability to process B vitamins
  • Who participated: 240 people total: 120 people diagnosed with Alzheimer’s disease and 120 healthy people of similar age without memory problems
  • Key finding: People carrying certain MTHFR gene variations had 3-4 times higher risk of Alzheimer’s compared to those without these variations. They also had higher levels of homocysteine (a harmful substance) and lower B vitamin levels in their blood.
  • What it means for you: If you have a family history of Alzheimer’s, knowing your MTHFR gene type might help your doctor assess your risk. Taking B vitamins (B6, B12, and folate) and keeping homocysteine levels low through diet and supplements may be protective, though more research is needed to confirm this.

The Research Details

This was a case-control study, which is like comparing two groups of people: those who have a disease and those who don’t. Researchers looked at 120 people with Alzheimer’s disease and 120 healthy people without memory problems. They tested everyone’s genes to find the MTHFR variations, measured their blood levels of homocysteine and B vitamins, and gave them memory tests. They also looked at brain scans to see if there were any differences in brain structure between the two groups.

The researchers used a special genetic test called TaqMan SNP assays to identify which version of the MTHFR gene each person had. They measured homocysteine, folate (vitamin B9), and vitamin B12 levels in everyone’s blood. Memory was tested using two different scales: the Hindi Mini-Mental State Examination and the Hindi Mattis Dementia Rating Scale. Brain imaging (MRI) was used to look for white matter changes and shrinkage in the brain.

After collecting all this information, scientists used computer analysis to understand how the MTHFR gene connects to other genes known to affect Alzheimer’s risk. This helped them figure out the biological pathways that might explain why this gene variant increases Alzheimer’s risk.

Case-control studies are valuable because they let researchers quickly identify risk factors by comparing people who already have a disease with those who don’t. This approach is especially useful for studying diseases like Alzheimer’s that develop slowly over many years. By measuring both genes and blood chemicals, this study provides evidence that connects genetic variations to real biological changes in the body, making the findings more convincing.

This study has several strengths: it measured multiple related factors (genes, blood chemicals, memory, and brain imaging), used standardized memory tests, and included a control group of healthy people for comparison. However, the study was conducted in one location with a specific population, so results may not apply equally to all ethnic groups. The study is relatively recent (2025) and published in a peer-reviewed journal, which adds credibility. One limitation is that this is observational research, so it shows association but not definite cause-and-effect.

What the Results Show

People with Alzheimer’s disease had significantly higher levels of homocysteine in their blood and lower levels of folate and vitamin B12 compared to healthy people. This suggests their bodies are not processing B vitamins efficiently. When researchers looked at the MTHFR gene, they found that people with certain variations (C677T and A1298C) had 3-4 times higher risk of developing Alzheimer’s compared to those without these variations.

The study found that people carrying the risk-associated gene versions showed the most pronounced metabolic problems: the highest homocysteine levels, the lowest B vitamin levels, and the worst memory test scores. Brain imaging showed that these individuals also had more white matter changes (areas of damage in the brain’s communication pathways) and more brain shrinkage.

Using computer analysis, researchers discovered that the MTHFR gene works together with several other genes known to affect Alzheimer’s risk, including genes called APP, PSEN1/2, MAPT, APOE, CLU, PICALM, and SORL1. This suggests that MTHFR doesn’t work alone but is part of a larger network of genetic factors that influence Alzheimer’s development.

The study found that people with Alzheimer’s also had higher blood glucose levels, suggesting problems with blood sugar control. Brain imaging revealed specific patterns of damage in white matter (the brain’s communication highways) and cortical atrophy (shrinkage of the brain’s outer layer). The bioinformatics analysis showed that the MTHFR gene affects three main biological pathways: one-carbon metabolism (how the body processes B vitamins), oxidative stress defense (the body’s ability to fight harmful molecules), and vascular pathways (blood vessel function). These findings suggest multiple ways that the MTHFR gene variant could damage the brain.

Previous research has suggested that high homocysteine levels are linked to Alzheimer’s risk, and that B vitamin deficiencies may contribute to cognitive decline. This study builds on that work by identifying a specific genetic reason why some people accumulate homocysteine: variations in the MTHFR gene that reduce its efficiency. The findings align with earlier studies showing that MTHFR variants affect how the body processes B vitamins, but this is one of the first studies to directly connect these gene variants to Alzheimer’s risk in this particular population.

This study has several important limitations. First, it only included 240 people from what appears to be a specific geographic region, so the results may not apply equally to all populations worldwide. Second, because this is a case-control study, it shows that the gene variant is associated with Alzheimer’s but doesn’t prove it causes Alzheimer’s—people with the variant might have other risk factors. Third, the study is observational, meaning researchers couldn’t control all the factors that might influence results, such as diet, exercise, or other lifestyle factors. Fourth, this study was published very recently (2025), so other scientists haven’t yet had time to confirm these findings in other populations. Finally, the study doesn’t tell us whether taking B vitamins would actually prevent Alzheimer’s in people with these gene variants.

The Bottom Line

If you have a family history of Alzheimer’s disease, consider asking your doctor about testing for MTHFR gene variants (moderate confidence). If you carry the risk variants, maintaining adequate B vitamin intake through diet or supplements may be beneficial, though this needs further research (low to moderate confidence). Keep homocysteine levels low by eating foods rich in B vitamins (leafy greens, eggs, fish, legumes) and maintaining a healthy lifestyle (moderate confidence). Regular cognitive screening and brain health monitoring may be appropriate for those with genetic risk factors (moderate confidence).

This research is most relevant for people with a family history of Alzheimer’s disease, especially those concerned about their own risk. It may also interest people over age 50, as Alzheimer’s risk increases with age. Healthcare providers, particularly neurologists and geriatricians, should be aware of these findings when assessing Alzheimer’s risk. People with elevated homocysteine levels should pay special attention. However, having the MTHFR variant doesn’t mean you will definitely develop Alzheimer’s—many people with these variants never develop the disease.

If you make changes based on this research, you likely won’t see dramatic changes in memory or cognition quickly. B vitamin supplementation and lifestyle changes typically take months to years to show effects on brain health. Cognitive decline in Alzheimer’s happens gradually over years or decades, so prevention strategies need to be maintained long-term. Brain imaging changes might be detectable within 1-2 years of intervention, but memory improvements could take longer.

Want to Apply This Research?

  • Track weekly B vitamin intake (B6, B12, folate) through food and supplements, aiming for recommended daily amounts. Log homocysteine levels if tested by your doctor every 6-12 months. Record monthly cognitive check-ins using simple memory tests or brain training apps.
  • Users can set daily reminders to eat B-vitamin-rich foods (eggs, spinach, salmon, chickpeas) and take supplements if recommended by their doctor. Create a weekly meal plan featuring foods high in folate, B12, and B6. Set reminders for annual or semi-annual homocysteine blood tests if you have risk factors.
  • Establish a baseline by getting homocysteine, folate, and B12 levels tested now. Retest every 6-12 months to track changes. Use the app to log any changes in memory, concentration, or mental clarity. Track adherence to B vitamin supplementation and dietary changes. If available, compare results over time to see if interventions are working.

This research suggests an association between MTHFR gene variants and Alzheimer’s risk but does not prove causation. These findings are from a single study and have not yet been confirmed by other researchers. This information is for educational purposes only and should not replace professional medical advice. If you have concerns about Alzheimer’s risk or cognitive changes, consult with your healthcare provider or a neurologist. Do not start or stop any supplements or medications based solely on this research without discussing it with your doctor first. Genetic testing should only be done under medical supervision with appropriate genetic counseling.