Epigenetic Marker in Blood May Help Detect Alzheimer’s

According to the Alzheimer’s Association, 47 million people worldwide are living with Alzheimer’s. But since it can take 20 years for brain changes to accumulate into the symptoms that lead to diagnosis, effective intervention can be difficult. Even diagnosis itself poses a challenge, with only one out of every four people suffering from Alzheimer’s actually receiving a diagnosis. This is why scientists have been looking to find anything they can leverage to help pinpoint which patients are more likely to have the disease.

A research team headed by Professor Andrea Fuso of the Sapienza University of Rome sought to find a biomarker that could be useful to diagnosing and treating Alzheimer’s. Having previously worked with Presenilin1 (PSEN1), they had shown that DNA methylation could affect PSEN1 expression, which could affect subsequent amyloid protein production in the brain. Mutations in PSEN1 are known to lead to the development of Alzheimer’s disease, leading to the formation of the amyloid plaques that are characteristic of affected individuals.

Instead of looking at changes in the DNA sequence itself, Professor Fuso’s team looked for changes in DNA methylation in samples. As the field of epigenetics continues to show each day, modifications to the genetic code can either open or close the DNA to transcriptional machinery, resulting in altered gene expression.

The team examined human post-mortem brain tissue samples in adults with Alzheimer’s, as well as controls that included both healthy babies and adolescents. Blood samples from 20 adults with late-onset Alzheimer’s were compared to healthy controls to see if DNA methylation changes could be detected in the blood, which could offer a potential avenue for minimally invasive testing. 

They began by looking at DNA modifications, comparing both sexes of normal healthy mice with Alzheimer’s-prone mice. Adult female mice showed overexpression of the PSEN1 gene that correlated with reduced DNA methylation, although sex-specific differences couldn’t be properly measured in humans due to the limited sample size. Overall, the same inverse relationship between gene expression and DNA methylation was detected.

Professor Fuso notes, “Differences between the sexes in DNA modifications would be extremely interesting to researchers working to better understand Alzheimer’s disease and to develop new therapies.”

Perhaps even more significantly, the differences in expression levels were evident in blood samples. Patients with Alzheimer’s showed detectably lower methylation of PSEN1 in their blood than healthy controls, although the difference was not quite as large as observed in brain samples. However, the detection of significant differences in methylation means that this test could potentially be used to diagnose Alzheimer’s in patients less invasively than, say, requiring brain samples.

Professor Fuso goes on to say, “Our results offer an exciting new area of investigation, deploying the methods we used to study DNA methylation so that modifications won’t be missed. If found to be causal, our findings would provide a starting point for developing epigenetic therapies.” Indeed, while minimally invasive detection is helpful, so would be the capacity to intervene epigenetically and stop the development of Alzheimer’s early in its course.

One of the first steps for researchers to undertake next will be to replicate this study in larger sample cohorts, which could help determine if their findings persist across larger sample sizes. The conduction of parallel brain and blood analyses will help evaluate the accuracy and reliability of the findings. Professor Fuso’s team also recommends the examination of methylation data within the context of environmental influencers of methylation, which include B vitamins, homocysteine, and S-adenosylhomocysteine.

Source: Fuso, A. et al. (2020). CpG and non-CpG Presenilin1 methylation pattern in course of neurodevelopment and neurodegeneration is associated with gene expression in human and murine brainEpigenetics.

Reference: Taylor & Francis Group. Could new discovery play a role in diagnosing Alzheimer’s earlier? TFG Press Releases. 7 Feb. 2020. Web.

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About Andrea P 30 Articles
Andrea received her B.S. in Biology with minors in Chemistry and Neuroscience from Duke University. She first fell in love with biology when she learned about the magnificent powers of protein folding, and then naturally wanted to know who was in charge. She’s fascinated by the finer controls of epigenetic modifications. In her downtime, she enjoys hiking with her dog and going for long drives to explore new places.


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