DNA strand merging into a brain scan highlighting medial temporal lobe with Alzheimer's risk genes.

Unlocking Alzheimer's: Can Genetics & Brain Scans Predict Your Risk?

Jordan Keane in Health & Wellness December 2025 • 4 min read.

"New research explores how TOMM40 gene variants and brain imaging could help identify Alzheimer's risk in healthy adults."

Alzheimer's disease (AD) is a complex condition influenced by both genetic and environmental factors. While genes like APOE are known to play a role, they don't fully explain who will develop AD. Researchers are constantly searching for new ways to identify people at risk, even before symptoms start.

One promising area of research involves the TOMM40 gene, which is linked to APOE and may affect how brain cells function. Scientists are also using brain imaging techniques, like FDDNP-PET scans, to visualize the buildup of plaques and tangles in the brain – hallmarks of Alzheimer's.

A new study explores whether specific variations in the TOMM40 gene, combined with brain imaging results, can help predict Alzheimer's risk in healthy older adults. This article breaks down the study's findings and explains what they could mean for the future of Alzheimer's prevention and treatment.

Decoding TOMM40: How Gene Length Impacts Alzheimer's Risk

DNA strand merging into a brain scan highlighting medial temporal lobe with Alzheimer's risk genes.

The TOMM40 gene provides instructions for making a protein that helps transport other proteins into mitochondria. Mitochondria are the powerhouses of our cells. The length of a specific section within the TOMM40 gene, called the 'poly-T' region, varies from person to person. Prior research has suggested the length of this poly-T region could be associated with a person's risk of developing Alzheimer's.

In this study, researchers looked at the relationship between TOMM40 poly-T length, brain imaging results, and cognitive function in a group of non-demented older adults. Participants were categorized based on their TOMM40 poly-T length (short, long, or very long) and whether or not they carried the APOE4 gene, another well-known Alzheimer's risk factor.

The study used FDDNP-PET scans to measure the levels of plaque and tangle deposits in the medial temporal lobe (MTL), a brain region affected early in Alzheimer's disease.
Researchers then analyzed how TOMM40 and APOE4 gene variants correlated with plaque and tangle buildup in the MTL, as well as with cognitive performance on memory, language, attention, and executive function tests.

The key finding was that individuals with longer TOMM40 poly-T lengths, but without the APOE4 gene, had higher levels of plaque and tangle deposits in the MTL compared to those with shorter TOMM40 poly-T lengths. This suggests that TOMM40 may independently contribute to Alzheimer's-related brain changes, even in the absence of the better-known APOE4 risk.

What Does This Mean for You? The Future of Alzheimer's Prediction

This research offers a glimpse into the potential for using genetic information and brain imaging to identify individuals at increased risk of Alzheimer's disease, even before they experience any noticeable symptoms. This could be important because treatments are most effective when started early.

The study highlights the complex interplay of genes in Alzheimer's and also reinforces that AD is a highly heterogeneous disorder, and neither genetic nor imaging markers alone are likely to be useful in definitively predicting who will develop AD. The current finding that FDDNP binding is related to a genetic risk factor for AD may imply that there are changes in the brain that may be phenotypic in prodromal AD.

While more research is needed, these findings suggest that we may one day be able to develop personalized risk assessments based on an individual's genetic makeup, brain imaging results, and lifestyle factors. This could lead to earlier interventions, more targeted treatments, and ultimately, a better chance of preventing or delaying the onset of Alzheimer's disease.

About this Article -

This article was crafted using a human-AI hybrid and collaborative approach. AI assisted our team with initial drafting, research insights, identifying key questions, and image generation. Our human editors guided topic selection, defined the angle, structured the content, ensured factual accuracy and relevance, refined the tone, and conducted thorough editing to deliver helpful, high-quality information.See our About page for more information.

This article is based on research published under:

DOI-LINK: 10.1371/journal.pone.0208358, Alternate LINK

Title: Longer Tomm40 Poly-T Variants Associated With Higher Fddnp-Pet Medial Temporal Tau And Amyloid Binding

Subject: Multidisciplinary

Journal: PLOS ONE

Publisher: Public Library of Science (PLoS)

Authors: Prabha Siddarth, Alison C. Burggren, David A. Merrill, Linda M. Ercoli, Zanjbeel Mahmood, Jorge R. Barrio, Gary W. Small

Published: 2018-12-05

Everything You Need To Know

How might the length of the TOMM40 gene's poly-T region influence my chances of developing Alzheimer's?

The TOMM40 gene contains a section called the 'poly-T' region. The length of this region varies between individuals. Research suggests that the length of the TOMM40 poly-T region could be related to a person's likelihood of developing Alzheimer's. Individuals with longer poly-T lengths may have a higher risk, especially when considered alongside other genetic factors like the absence of the APOE4 gene. Further research is needed to fully understand this relationship and how it interacts with other risk factors.

If I don't have the APOE4 gene, can variations in the TOMM40 gene still impact my risk for Alzheimer's?

APOE4 is a gene known to increase the risk of Alzheimer's. The recent study showed that individuals with longer TOMM40 poly-T lengths had higher levels of plaque and tangle deposits in the medial temporal lobe (MTL) even without the APOE4 gene. This suggests TOMM40 can independently contribute to Alzheimer's related brain changes even without the influence of APOE4. It highlights the complex interplay of multiple genetic factors in influencing Alzheimer's risk.

What exactly does an FDDNP-PET scan reveal about the brain in relation to Alzheimer's disease?

FDDNP-PET scans are a brain imaging technique used to visualize the buildup of plaques and tangles in the brain, which are hallmarks of Alzheimer's. In this study, FDDNP-PET scans were used to measure the levels of plaque and tangle deposits in the medial temporal lobe (MTL) of study participants. By combining FDDNP-PET scan data with genetic information like TOMM40 poly-T length and the presence of the APOE4 gene, researchers can better assess an individual's risk of developing Alzheimer's.

Why is the medial temporal lobe (MTL) so important when evaluating Alzheimer's risk?

The medial temporal lobe (MTL) is a brain region that is affected early in Alzheimer's disease. The study found that individuals with longer TOMM40 poly-T lengths, in the absence of the APOE4 gene, had higher levels of plaque and tangle deposits in the MTL. This finding suggests that TOMM40 may play a role in the early development of Alzheimer's-related changes in the brain. Detecting changes in the MTL through brain imaging could be an important early indicator of Alzheimer's risk.

What are the potential benefits of identifying Alzheimer's risk factors like TOMM40 gene variants and brain plaque buildup before symptoms even appear?

Identifying individuals at increased risk of Alzheimer's disease, even before they experience noticeable symptoms, could allow for earlier interventions and treatments. Early detection of elevated risk, through methods like assessing TOMM40 gene variants combined with brain imaging such as FDDNP-PET scans, can inform preventative strategies. Though not discussed in the text, this may include lifestyle changes, cognitive training, or future medications aimed at slowing down or preventing the onset of the disease. This also opens doors to clinical trials for new treatments.