New tools could uncover important answers for Alzheimer's researchers

April 30, 2018 by Jeff Sossamon, University of Missouri-Columbia
(A) Immunohistochemistry using 6E10 antibody against Aβ showing various sizes of dense Aβ plaques (white arrow heads); (B) Adjacent brain section that was used for immunohistochemistry using an antibody against Tau showing dense Aβ plaques also contained Tau (arrow heads). Necrotic neurons that were stained dark blue were not Aβ or Tau positive (arrows); (C) The presence of Aβ plaques under the alveolus hippocampus (Alv) and hippocampal fissure (arrow heads). Credit: Yuksel Agca, MU College of Veterinary Medicine publishing in PLOS ONE

Alzheimer's disease currently affects more than 5.5 million Americans and is one of the costliest diseases to treat, according to the Alzheimer's Association. Characterized by a buildup of plaque in the brain, few animal models exist that researchers could use to study this devastating disorder. Now, a team of researchers from the University of Missouri, publishing in PLOS ONE, developed a rat model that can be used to study the buildup of amyloid plaques and vascular abnormalities in the brain.

"One of the defining traits of Alzheimer's is the progressive accumulation of amyloid-β plaques in the ," said Yuksel Agca, associate professor of veterinary pathology and a researcher in the Comparative Medicine Program in the MU College of Veterinary Medicine. "Two proteins, APP and PS1 are linked to the development of Alzheimer's disease in humans—and these two targets have become the basis for numerous studies. If we can identify how to manipulate amyloid-β build up, we can reduce the production of harmful plaques in the brain, leading to decreases in the onset of Alzheimer's disease."

The MU researchers developed rats that had human APP and PS1 proteins. The rats then underwent behavioral assessments in the Barnes maze. The maze, which tracks rodent behavior is used to measure learning and spatial memory. In a series of experiments, the Alzheimer's model rats that produced human APP and PS1 displayed poor memory and learning.

After the maze experiments, the research team assessed amyloid-β levels through serum tests, as well as brain screenings, which showed vascular changes and amyloid-β plaques similar to the ones observed in humans suffering from Alzheimer's disease.

"We found that these rat models could be useful in the fight against Alzheimer's in people," Agca said. "Because of their shorter lifespans and their larger size, translational models such as rats are extremely helpful in ongoing studies of disease. The results can be translatable to humans in identifying targets for drugs as well as identifying everyday lifestyle changes we can make to help stave off disorders like Alzheimer's. We hope this model will become beneficial as research continues to move forward."

Just like plaque on teeth or in arteries, in the brain can be decreased in people by maintaining a good diet and exercise, Agca said.

The study, "Memory deficiency, , and amyloid-β plaques in APP+PS1 double transgenic of Alzheimer's disease," was published in PLOS ONE.

Explore further: Alzheimer's drug targeting soluble amyloid falls short in a large clinical trial

More information: Diana Klakotskaia et al. Memory deficiency, cerebral amyloid angiopathy, and amyloid-β plaques in APP+PS1 double transgenic rat model of Alzheimer's disease, PLOS ONE (2018). DOI: 10.1371/journal.pone.0195469

Related Stories

Alzheimer's drug targeting soluble amyloid falls short in a large clinical trial

January 25, 2018
A paper published today in the New England Journal of Medicine reports that solanezumab, a monoclonal antibody-based treatment for Alzheimer's disease developed by Eli Lilly that targets amyloid plaques, did not significantly ...

Researchers identify possible treatment window for memory problems

February 27, 2013
Researchers have identified a possible treatment window of several years for plaques in the brain that are thought to cause memory loss in diseases such as Alzheimer's. The Mayo Clinic study is published in the Feb. 27 online ...

Saving neurons may offer new approach for treating Alzheimer's disease

November 6, 2017
Treatment with a neuroprotective compound that saves brain cells from dying also prevents the development of depression-like behavior and the later onset of memory and learning problems in a rat model of Alzheimer's disease. ...

New connection sprouts between Alzheimer's disease and the immune system

May 31, 2017
Just as trimming back the branches of an overgrown plant can encourage healthy growth, a little pruning of the connections in the human brain can be a good thing during brain development. But what happens when this natural ...

Carmustine decreases amyloid beta plaques

March 25, 2013
Long term treatment by carmustine, a chemical relative of mustard gas and already used to treat some types of brain cancer, can decrease the amount of amyloid β and number of amyloid plaques in a mouse model of Alzheimer's ...

'Pac-Man' gene implicated in Alzheimer's disease

July 26, 2016
A gene that protects the brain from the harmful build-up of amyloid-beta, one of the causative proteins implicated in Alzheimer's disease, has been identified as a new target for therapy by NeuRA researchers.

Recommended for you

Meditation and music may alter blood markers of cellular aging and Alzheimer's disease

November 13, 2018
A research team led by Dr. Kim Innes, a professor in the West Virginia University School of Public Health, has found that a simple meditation or music listening program may alter certain biomarkers of cellular aging and Alzheimer's ...

Alzheimer's and cardiovascular disease share common genetics in some patients

November 9, 2018
Genetics may predispose some people to both Alzheimer's disease and high levels of blood lipids such as cholesterol, a common feature of cardiovascular disease, according to a new study by an international team of researchers ...

Artificial intelligence predicts Alzheimer's years before diagnosis

November 6, 2018
Artificial intelligence (AI) technology improves the ability of brain imaging to predict Alzheimer's disease, according to a study published in the journal Radiology.

Diabetes medications may reduce Alzheimer's disease severity

November 1, 2018
People with Alzheimer's disease who were treated with diabetes drugs showed considerably fewer markers of the disease—including abnormal microvasculature and disregulated gene expressions—in their brains compared to Alzheimer's ...

Massive study confirms that loneliness increases risk of dementia

October 29, 2018
A new Florida State University College of Medicine study involving data from 12,000 participants collected over 10 years confirms the heavy toll that loneliness can take on your health: It increases your risk of dementia ...

Bioactive compound from the Rhodiola plant improves memory

October 25, 2018
In an ageing society, more people are suffering from memory disorders. The progressive loss of memory severely impairs the quality of life of those affected. So far, no drugs are known to prevent age-related cognitive decline.

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.