Body's immune system may play larger role in Alzheimer's disease than thought

February 23, 2016, University of California, Irvine
Microglia (green) surround an amyloid plaque (blue) in the brain of an Alzheimer's disease mouse model. UCI researchers have shown that endogenous mouse antibodies (red) associate with microglia in the brains of such mice and boost microglia's ability to degrade plaques. Credit: Samuel Marsh / UCI

Immune cells that normally help us fight off bacterial and viral infections may play a far greater role in Alzheimer's disease than originally thought, according to University of California, Irvine neurobiologists with the Sue & Bill Gross Stem Cell Research Center and the Institute for Memory Impairments and Neurological Disorders.

The researchers discovered this when Alzheimer's disease genetically modified to lack these key in their blood developed the distinctive plaques associated with the neurodegenerative disorder much more quickly.

According to Mathew Blurton-Jones, assistant professor of neurobiology & behavior, and doctoral student Samuel Marsh, their findings could lead to the creation of new techniques to help identify, or perhaps even treat, individuals at risk of developing the disease.

Alzheimer's is the leading cause of age-related dementia and is thought to be driven by the accumulation of a protein called beta-amyloid that aggregates to form amyloid plaques in the brain. Microglia, immune cells that reside in the brain, attempt to clear this buildup, but in Alzheimer's, they appear to be fighting a losing battle. While many studies have explored the role of microglia in Alzheimer's, very few researchers have asked whether a different set of immune cells called T-cells and B-cells that reside outside the brain and play a large part in autoimmune diseases might also impact Alzheimer's.

To test this idea, Blurton-Jones and Marsh bred genetically modified Alzheimer's disease mice to lack three key immune cell types: T-cells, B-cells and NK-cells. Six months later, when the brains of these mice were compared to those of Alzheimer's mice with intact immune systems, the scientists found a more than twofold increase in beta-amyloid accumulation.

"We were very surprised by the magnitude of this effect," Blurton-Jones said. "We expected the influence of the deficient on Alzheimer's pathology to be much more subtle."

To understand how the loss of these immune cells was increasing beta-amyloid, he and Marsh examined the interactions between these peripheral cells and microglia within the brain.

"We found that in Alzheimer's mice with intact immune systems, antibodies - which are made by B-cells - accumulated in the brain and associated with microglia. This, in turn, helped increase the clearance of beta-amyloid," Marsh said.

To further confirm the importance of this interplay between immune cells in the blood and those in the brain, the researchers transplanted healthy bone marrow stem cells into the immune-deficient Alzheimer's mice. Since T-, B- and NK-cells develop from bone marrow stem cells, this transplantation led to a reconstitution of the missing immune cells. This allowed the B-cells to produce antibodies that once again reached the brain and aided microglia in eradicating the beta-amyloid.

"We know that the immune system changes with age and becomes less capable of making T- and B-cells," Blurton-Jones said. "So whether aging of the immune system in humans might contribute to the development of Alzheimer's is the next big question we want to ask."

Explore further: Brain's immune system could be harnessed to fight Alzheimer's

Related Stories

Brain's immune system could be harnessed to fight Alzheimer's

November 4, 2015
A new study appearing in the Journal of Neuroinflammation suggests that the brain's immune system could potentially be harnessed to help clear the amyloid plaques that are a hallmark of Alzheimer's disease.

Immune cells are an ally, not enemy, in battle against Alzheimer's

January 29, 2015
Beta-amyloid is a sticky protein that aggregates and forms small plaques in the brains of the elderly and is thought to be a cause of Alzheimer's disease. Because specialized immune cells always surround these plaques, many ...

Modified stem cells offer potential pathway to treat Alzheimer's disease

April 15, 2014
UC Irvine neurobiologists have found that genetically modified neural stem cells show positive results when transplanted into the brains of mice with the symptoms and pathology of Alzheimer's disease. The pre-clinical trial ...

Researchers target immune system in hunt for new Alzheimer's treatments

August 19, 2015
Researchers in Israel have manipulated the mouse immune system to target Alzheimer's disease. The research was published in the journal Nature Communications on 18 August 2015.

Study shows beneficial effects of blocking brain inflammation in experimental model of Alzheimer's

January 7, 2016
A University of Southampton-led study has found that blocking a receptor in the brain responsible for regulating immune cells could protect against the memory and behaviour changes seen in the progression of Alzheimer's disease.

Hyperactive neurons may be culprit in Alzheimer's

January 13, 2016
A long-term reduction in neuronal activity reduces amyloid plaques associated with Alzheimer's disease, Yale University researchers have found. The study, using mouse models of Alzheimer's, found the opposite is also true—triggering ...

Recommended for you

Not being aware of memory problems predicts onset of Alzheimer's disease

February 15, 2018
Doctors who work with individuals at risk of developing dementia have long suspected that patients who do not realize they experience memory problems are at greater risk of seeing their condition worsen in a short time frame, ...

Poor fitness linked to weaker brain fiber, higher dementia risk

February 14, 2018
Scientists have more evidence that exercise improves brain health and could be a lifesaving ingredient that prevents Alzheimer's disease.

Compound prevents neurological damage, shows cognitive benefits in mouse model of Alzheimer's disease

February 7, 2018
The supplement nicotinamide riboside (NR) – a form of vitamin B3 – prevented neurological damage and improved cognitive and physical function in a new mouse model of Alzheimer's disease. The results of the study, conducted ...

Positive attitudes about aging reduce risk of dementia in older adults

February 7, 2018
Research has shown that older persons who have acquired positive beliefs about old age from their surrounding culture are less likely to develop dementia. This protective effect was found for all participants, as well as ...

One in five older adults experience brain network weakening following knee replacement surgery

February 7, 2018
A new University of Florida study finds that 23 percent of adults age 60 and older who underwent a total knee replacement experienced a decline in activity in at least one region of the brain responsible for specific cognitive ...

Redefined Alzheimer's biology has implications for drug design

February 7, 2018
Despite the 25-year focus on the build-up in brain tissues of one protein, amyloid beta, as the purported origin of Alzheimer's disease (AD), a new study argues that it is likely triggered instead by the failure of a system ...

1 comment

Adjust slider to filter visible comments by rank

Display comments: newest first

Daggett
not rated yet Feb 23, 2016
When caring for older women- I always wondered if husband gave them STD's that caused it!

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.