Genes at play: uncovering the link between DNA changes and Alzheimer’s

Genes are key to our existence, and their activity goes through a robust regulation mechanism. One of these mechanisms, DNA methylation, is vital in producing proteins. Any irregularity in this process could manifest as cancer, atherosclerosis, nervous disorders, and cardiovascular or neurological conditions.   

A recent study published in Alzheimer’s & Dementia, the journal of the Alzheimer’s Association, has shown that some changes in DNA methylation influence Alzheimer-related genes, which could increase the risk of developing the condition. 

“DNA methylation directly regulates neuroinflammation and neurodegeneration in individuals with Alzheimer’s and is a key factor affecting its progression,” Dr Bin Zhang, research professor of neurogenetics at Mount Sinai Center for Transformative Disease Modeling, USA, tells Happiest Health. 

When patterns go awry 

Responses to cell activity are regulated by proteins with specific DNA strands. These strands control the action of a gene to produce proteins. This is done by a chemical process in which a molecule called a methyl group is attached to the DNA strand at a specific location. However, errors can occur if the molecule is attached to a different region. This alters the gene’s chemical pattern and causes it to miss the correct steps. This results in the production of incorrect proteins and a change in gene activity.  

Studies have already established that changes in DNA methylation can alter gene activity, increasing the risk of developing diseases. For instance, a 2018 study demonstrated that methylation alterations of the APOE4 gene can lead to Alzheimer’s. Yet, the exact steps of these changes remained unclear.  

Read more: Decoding the genetics of Alzheimer’s: the role of APOE4 and SHMOOSE 

In the present study, the Mount Sinai researchers  investigated the effect of DNA methylation alteration in Alzheimer’s condition. 

Uncovering new patterns  

They initially studied brain tissue from 196 deceased individuals with healthy brains, mild cognition impairment, or Alzheimer’s. They then focused on the parahippocampal gyrus, where memory processing and gene activity changes occur.  

The researchers performed gene analysing techniques on the brain samples and checked the effect of methylation alterations in the brain. They found 270 new methylation patterns on the DNA of those who had Alzheimer’s. These new patterns were affecting gene activity and causing Alzheimer’s compared to those samples of healthy individuals.  

“Now we know that DNA methylation is one key driving force for hundreds and thousands of molecular changes and complex gene and protein interaction networks in the brains of [those with] Alzheimer’s,” says Dr Zhang. 

Similar changes in methylation patterns were observed when the sample size was increased to 713. Dr Zhang says these changes express prominently and dysregulate the specific Alzheimer’s gene function, establishing that DNA methylation is a crucial influencer of the condition. 

“We have paid more attention to the genetics of Alzheimer’s and changes in individual genes and proteins as well as gene/protein interacting networks in Alzheimer’s,” he adds. 

The study could lead to the development of novel gene-based medicines, says Dr Zhang.  

The next research step is to more closely analyse the new 270 DNA methylation patterns in stem cells (iPSC) and mice to gain insight into the progression of the disease.  

Read more: How disease-in-a-dish model could help treat brain disorders