Research on advanced Alzheimer's disease investigates novel ways to restore cognitive function

June 27, 2017 by Ellen Goldbaum, University at Buffalo
Credit: Wikimedia Commons

While most research on Alzheimer's disease (AD) has focused on early diagnosis and treatment, University at Buffalo scientists are studying genetic and epigenetic factors with the ultimate goal of restoring function to patients in the later stages of the disease.

The UB team's research will include studies in mouse models carrying gene mutations for familial AD (where more than one member of a family has the disease) and in human stem cell-derived neurons from AD patients.

Zhen Yan, PhD, principal investigator, and Jian Feng, PhD, co-investigator, both professors in the Department of Physiology and Biophysics in the Jacobs School of Medicine and Biomedical Sciences at UB, have received a five-year, $2 million grant from the National Institutes of Health to conduct preclinical research to tease out genetic and epigenetic factors that cause Alzheimer's disease. Epigenetic factors can change by altering the way that gene promoters, which initiate the copying of genetic information known as transcription, access the cellular machinery that conducts transcription. Such changes may profoundly impact human health.

"We hypothesize that Alzheimer's is produced by a combination of and environmental factors, such as aging," said Yan, "that induce the dysregulation of specific epigenetic processes that, in turn, lead to impaired cognition."

The UB research will explore how that accompany Alzheimer's disease also might help identify a much sought-after biomarker for the disease, which could, in turn, allow for novel treatment.

Numerous clinical trials in recent years have focused on reducing amyloid beta plaque in the brain. So far, such efforts haven't yet translated into improving cognitive function, Yan said.

"Our research, by contrast, will target synaptic function, which is at the root of cognitive function," she explained. "The idea is that this approach will have a more fundamental effect."

She and her colleagues will investigate aberrant histone methylation, an epigenetic process that affects the expression of genes encoding key proteins that allow for signals to be transmitted between neurons.

When this process is dysregulated in Alzheimer's disease, neuronal signaling doesn't function properly, leading to cognitive impairment.

As those with loved ones with Alzheimer's know, even though the patient can easily remember something that happened 20 years ago, the later stages are characterized by a growing inability to recall recently learned information. That kind of short-term memory, Yan explained, is dependent on excitatory transmission in the frontal cortex, mediated by glutamate receptors.

"At the later stages of the , we know that there is a loss of glutamate receptors that are crucial for learning and memory," she said. "When these receptors lose the ability to communicate, there is a loss of cognition. Our research will try to restore gene expression in these glutamate receptors using epigenetic tools, with the ultimate goal of restoring cognitive ."

Explore further: Researchers discover an epigenetic lesion in the hippocampus of Alzheimer's

Related Stories

Researchers discover an epigenetic lesion in the hippocampus of Alzheimer's

January 21, 2014
Alzheimer's disease can reach epidemic range in the coming decades, by the increasing average age of society. There are two key issues for Alzheimer's disease: there is currently no effective treatment and it has been described ...

Antibiotic restores cell communication in brain areas damaged by Alzheimer's disease

November 15, 2016
New research from the Djavad Mowafaghian Centre for Brain Health at UBC has found a way to partially restore brain cell communication around areas damaged by plaques associated with Alzheimer's disease.

Changes in genetic function in the brain linked to Alzheimer's

April 20, 2012
Changes in the epigenome, a structure that controls the function of genes, were found in the brains of Alzheimer's patients.

Epigenetic culprit in Alzheimer's memory decline

February 29, 2012
In a mouse model of Alzheimer's disease, memory problems stem from an overactive enzyme that shuts off genes related to neuron communication, a new study says.

Could blood pressure drugs have a role in Alzheimer's disease treatment?

January 29, 2016
In laboratory neuronal cultures, an FDA-approved drug used to treat high blood pressure reduced cell damage often linked to Alzheimer's disease, say researchers at Georgetown University Medical Center (GUMC) and the National ...

Recommended for you

Exercise may delay cognitive decline in people with rare Alzheimer's disease

September 25, 2018
For individuals carrying a genetic mutation that causes Alzheimer's disease, engaging in at least 2.5 hours of physical activity per week may have beneficial effects on markers of Alzheimer's disease brain changes and may ...

A biomarker in the brain's circulation system may be Alzheimer's earliest warning

September 24, 2018
USC scientists say Alzheimer's could be diagnosed earlier if scientists focus on an early warning within the brain's circulation system.

In landmark study, doctors say test identifies people most likely to get Alzheimer's

September 24, 2018
The beginning was the worst. It frustrated Janet Parkerson when her father started to forget what he had done that day or the day before.

Study clarifies ApoE4's role in dementia

September 20, 2018
ApoE4, a protein linked to both Alzheimer's disease and a form of dementia caused by damage of blood vessels in the brain, increases the risk of cognitive impairment by reducing the number and responsiveness of blood vessels ...

Machine learning IDs markers to help predict Alzheimer's

September 19, 2018
Nearly 50 million people worldwide have Alzheimer's disease or another form of dementia. These irreversible brain disorders slowly cause memory loss and destroy thinking skills, eventually to such an extent that self-care ...

Discovery could explain failed clinical trials for Alzheimer's, and provide a solution

September 19, 2018
Researchers at King's College London have discovered a vicious feedback loop underlying brain degeneration in Alzheimer's disease which may explain why so many drug trials have failed. The study also identifies a clinically ...

0 comments

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.