DNA methylation involved in Alzheimer's disease

August 17, 2014, Brigham and Women's Hospital
Diagram of the brain of a person with Alzheimer's Disease. Credit: Wikipedia/public domain.

A new study led by researchers at Brigham and Women's Hospital (BWH) and Rush University Medical Center, reveals how early changes in brain DNA methylation are involved in Alzheimer's disease. DNA methylation is a biochemical alteration of the building blocks of DNA and is one of the markers that indicate whether the DNA is open and biologically active in a given region of the human genome.

The study is published online August 17, 2014 in Nature Neuroscience.

According to the researchers, this is the first large-scale study employing epigenome-wide association (EWAS) studies—which look at chromosomal make-up and changes—in relation to the brain and Alzheimer's disease.

"Our study approach may help us to better understand the biological impact of and life experiences on Alzheimer's disease," said Philip L. De Jager, MD, PhD, Program in Translational Neuropsychiatric Genomics, BWH Departments of Neurology and Psychiatry, lead study author. "There are certain advantages to studying the epigenome, or the chemical changes that occur in DNA. The epigenome is malleable and may harbor traces of life events that influence disease susceptibility, such as smoking, depression and menopause, which may influence susceptibility to Alzheimer's and other diseases."

The researchers analyzed samples from 708 donated brains from subjects in the Religious Orders Study and Rush Memory and Aging Project, conducted by study co-author, David A. Bennett, MD, Rush Alzheimer's Disease Center in Chicago. They found that methylation levels correlated with Alzheimer's disease in 71 of 415,848 CpG markers analyzed (these are a pair of DNA building blocks consisting of a cytosine and a guanine nucleotide that are located next to each other). These 71 markers were found in the ANK1 and RHBDF2 genes, as well as ABCA7 and BIN1 which harbor known Alzheimer's disease susceptibility variants.

Further, investigation of these CpG associations revealed nearby genes whose RNA expression was altered in brain samples with Alzheimer's disease: ANK1, CDH23, DIP2A, RHBDF2, RPL13, RNF34, SERPINF1 and SERPINF2. This suggests that the CpG associations identify genes whose function is altered in Alzheimer's disease.

Further, "because these findings are also found in the subset of subjects that are not cognitively impaired at the time of death, it appears that these DNA methylation changes may play a role in the onset of Alzheimer's disease," said De Jager. "Moreover, our work has helped identify regions of the that are altered over the life-course in a way that is associated with Alzheimer's disease. This may provide clues to treating the disease by using drugs that influence epigenomic function."

Explore further: Potential biomarkers for the diagnosis of Alzheimer's disease

More information: Paper: dx.doi.org/10.1038/nn.3786
Related paper: dx.doi.org/10.1038/nn.3782

Related Stories

Potential biomarkers for the diagnosis of Alzheimer's disease

January 31, 2014
Researchers identify abnormal expression of genes, resulting from DNA relaxation, that can be detected in the brain and blood of Alzheimer's patients.

Decline in daily functioning related to decreased brain activity in Alzheimer's

August 12, 2014
Decline in daily functioning associated with Alzheimer's disease is related to alterations in activity in certain regions of the brain, according to a study published in the August 2014 issue of the Journal of Alzheimer's ...

Compounded outcomes associated with comorbid Alzheimer's disease, cerebrovascular disease

July 3, 2014
Researchers from the Sanders-Brown Center on Aging at the University of Kentucky have been able to confirm anecdotal information on patients with both Alzheimer's disease (AD) and cerebrovascular disease (CVD) using mouse ...

Researchers identify potential gene that may increase risk of ad in African Americans

August 4, 2014
Researchers from Boston University School of Medicine (BUSM) report that two rare variants in the AKAP9 gene significantly increase the risk of Alzheimer's disease (AD) in African-Americans.

Deciphering the DNA of Alzheimer's patients

December 4, 2013
(HealthDay)—Data that details every gene in the DNA of 410 people with Alzheimer's disease can now be studied by researchers, the U.S. National Institutes of Health announced this week.

New hope for treatment of Alzheimer's disease

July 15, 2014
Judes Poirier, PhD, C.Q., from the Douglas Mental Health Institute and McGill University in Montréal (Canada) and his team have discovered that a relatively frequent genetic variant actually conveys significant protection ...

Recommended for you

Rocky start for Alzheimer's drug research in 2018

January 19, 2018
The year 2018, barely underway, has already dealt a series of disheartening blows to the quest for an Alzheimer's cure.

Alzheimer's disease: Neuronal loss very limited

January 17, 2018
Frequently encountered in the elderly, Alzheimer's is considered a neurodegenerative disease, which means that it is accompanied by a significant, progressive loss of neurons and their nerve endings, or synapses. A joint ...

Anxiety: An early indicator of Alzheimer's disease?

January 12, 2018
A new study suggests an association between elevated amyloid beta levels and the worsening of anxiety symptoms. The findings support the hypothesis that neuropsychiatric symptoms could represent the early manifestation of ...

One of the most promising drugs for Alzheimer's disease fails in clinical trials

January 11, 2018
To the roughly 400 clinical trials that have tested some experimental treatment for Alzheimer's disease and come up short, we can now add three more.

Different disease types associated with distinct amyloid-beta prion strains found in Alzheimer's patients

January 9, 2018
An international team of researchers has found different disease type associations with distinct amyloid-beta prion strains in the brains of dead Alzheimer's patients. In their paper published in Proceedings of the National ...

Advances in brain imaging settle debate over spread of key protein in Alzheimer's

January 5, 2018
Recent advances in brain imaging have enabled scientists to show for the first time that a key protein which causes nerve cell death spreads throughout the brain in Alzheimer's disease - and hence that blocking its spread ...

4 comments

Adjust slider to filter visible comments by rank

Display comments: newest first

LaPortaMA
not rated yet Aug 17, 2014

Cause or effect?

Further, "because these findings are also found in the subset of subjects that are not cognitively impaired at the time of death, it appears that these DNA methylation changes may play a role in the onset of Alzheimer's disease, -- WHAT?
Caliban
3 / 5 (2) Aug 17, 2014

Cause or effect?

Further, "because these findings are also found in the subset of subjects that are not cognitively impaired at the time of death, it appears that these DNA methylation changes may play a role in the onset of Alzheimer's disease, -- WHAT?


@LaPortaMA,

The process seems to be complex, and dependent upon several factors leading to changes in the brain that add up to be Alzheimer's. Since some of the brains exhibited methylation without producing cognitive impairment(yet) in the donors, it is suspected that the donors simply hadn't developed the classic disease syndrome at the time of their death, but that -given time- they would have.

in answer to your question, you can think of methylation as "cause" -at least in part- but, it can also be considered effect, since it isn't yet clear what triggers the methylation events.

It's probably more helpful to think in terms of a chain of events(including some variability), rather than direct cause and effect.
JVK
1 / 5 (3) Aug 17, 2014
"...these CpG associations revealed nearby genes whose RNA expression was altered in brain samples..."

This suggests a clear link from ecological variation to nutrient-dependent changes in the microRNA/messenger RNA balance, which lead from alternative splicings of pre-mRNA to amino acid substitutions that differentiate the cell types of all individuals of all species from microbes to man via conserved molecular mechanisms.

The model that details the chain of events was first offered in the context of cell type differentiation and sex differences in cell types, which was before I realized that cell type differentiation must occur via conserved molecular mechanisms in all cells, of all tissues, of all organs, in all organ systems with the increasing organismal complexity manifested in nutrient-dependent pheromone-controlled morphological and behavioral phenotypes.

See: Nutrient-dependent/pheromone-controlled adaptive evolution: a model.
http://www.ncbi.n...24693353
animah
5 / 5 (3) Aug 17, 2014
Keep going scammer James V Kohl. Your SEO profile is slowly changing, and it won't stop until you stop spamming this board:

https://www.googl...+scammer

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.