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Large Epigenome Study Finds Hundreds Of Alzheimer's-Linked Sites

Published: Thursday, July 1, 2021 - 4:43pm
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Kaely Monahan/KJZZ
Diego Mastroeni, assistant research professor at ASU's Banner Neurodegenerative Disease Research Center.

The onset and advancement of Alzheimer’s disease (AD) is affected not only by a patient’s genes but also by the molecular switches that turn them on and off.

Now, one of the largest studies of these controls, know collectively as the epigenome, offers scores of possible AD treatment targets.

The meta-study, led by Katie Lunnon of the University of Exeter Medical School in the United Kingdom, appears in the journal Nature Communications.

Co-author Diego Mastroeni of the ASU-Banner Neurodegenerative Disease Research Center says the epigenome is a promising treatment toolkit because it’s far easier to manipulate than DNA.

“We've been studying all sorts of things for more than a hundred years now, and we still don't have any kind of therapy, really. So, maybe it's a good opportunity to look at different mechanisms.”

Data from more than 1,400 people across six studies revealed hundreds of genes turned on or off only in people with AD.

The locations of these epigenetic switches coincide with different AD phases called Braak stages. The six Braak stages categorize neurodegeneration according to the spread of AD's telltale neurofibrillary tangles through various areas of the brain.

The authors found 236 AD-related sites in the prefrontal cortex, a hub of executive functions and personality, and more than 100 in the temporal lobe, an area linked to sensory input, language and emotion.

But the authors found no such sites in the cerebellum, an area of the hindbrain associated with motor control and possibly some cognitive functions such as attention, language and emotional control.

"Really it's more associated with balance and things like that. Those are more Parkinson's-associated characteristics," said Mastroeni. 

Evolutionarily speaking, the cerebellum is the oldest part of the brain. Whether its apparent resistance is a consequence of its unusual structure or of some other built-in protection is unknown. But Mastroeni says even this area can be overtaken by the time a patient reaches Braak stage VI.

"During those stages, we do see some pathology creeping into the cerebellum," he said. 

"A lot of the individuals, you'd find them not moving so much in the bed any longer, really struggling, not being able to vocalize their thoughts."

Nearly 60% of dementia cases are due to AD. As of 2016, the disease affected 43.8 million people globally.

Scientists cannot yet say who is most at risk of developing the disease.

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