DNA methylation involved in Alzheimer's disease

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."

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

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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
5 / 5 (1) 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:

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