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

May 31, 2017, Brigham and Women's Hospital
High-resolution confocal images from the hippocampal CA3 region of Alzheimer's mouse brain show amyloid-beta plaques (green) and microglia/macrophages (red). Mice with complement C3 deficiency show an altered glial response to plaques. Credit: the Lemere Lab, Brigham and Women's Hospital

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 process goes wrong later in life? Investigators at Brigham and Women's Hospital have found new clues from preclinical models to indicate that this "synaptic refinement" may play a role in neurodegenerative disease. Their findings, published in Science Translational Medicine, offer new insights into the interplay between the immune system and the development of Alzheimer's disease.

The new study looks at the role of complement C3 - a molecule involved in the immune response that is elevated in Alzheimer's . Previous studies have shown that C3 helps to trim back the connections between brain cells - known as synapses - during normal . Synapse loss occurs early in Alzheimer's disease and is associated with cognitive decline. Researchers have not known whether blocking the "complement cascade" - of which C3 is a central part - could protect against impairment and neurodegeneration at later stages of the disease. In the new study, the team examined the effects of C3 deficiency in a mouse model for Alzheimer's disease. The team found that mice with the engineered C3 deficiency were protected against age-related loss of synapses and and had fewer markers of inflammation in the brain.

Interestingly, they also find that in aged mice, the telltale amyloid plaques of Alzheimer's disease remain - and are even more abundant - but cognitive function improved: mice performed better on a learning and memory task, despite the accumulation of plaque in the .

High-resolution confocal images from a C3-sufficient mouse model of Alzheimer's disease show macrophages (red), microglia (green), amyloid-beta plaques (blue) and a composite image of all three. C3 deficiency partially suppressed the glial response to plaques. Credit: Lemere Lab, Brigham and Women's Hospital

"Amyloid plaque deposition occurs years before memory loss in Alzheimer's disease, but targeting how the immune system responds to these plaques could be an excellent therapeutic approach," said corresponding author Cynthia Lemere, PhD, of the Ann Romney Center for Neurologic Diseases at BWH. "We think that in later stages of the disease, it's not necessarily the plaques but the immune system's response to them that leads to neurodegeneration."

C3 has also been implicated in other central nervous system conditions, including stroke and macular degeneration. Although the current study is limited by the differences in the immune system and life span of mice and humans, the team's findings - and clues from previous studies - suggest that modulating complement signaling may represent a potential therapeutic strategy for combating Alzheimer's disease.

Explore further: Study reveals the possibility of curbing synapse loss in Alzheimer's

More information: DOI: 10.1126/scitranslmed.aaf6295 Q. Shi el al., "Complement C3 deficiency protects against neurodegeneration in aged plaque-rich APP/PS1 mice," Science Translational Medicine (2017). http://stm.sciencemag.org/lookup/doi/10.1126/scitranslmed.aaf6295

Related Stories

Study reveals the possibility of curbing synapse loss in Alzheimer's

March 31, 2016
Researchers at Boston Children's Hospital show how brain connections, or synapses, are lost early in Alzheimer's disease and demonstrate that the process starts—and could potentially be halted—before telltale plaques ...

Alzheimer's disease researchers solve mystery of beguiling protein

February 6, 2017
Leading neuroscientists have clarified the role of a controversial immune system protein in Alzheimer's disease, showing it has opposing effects in early and late stages of the disease. Their discovery unites previous studies ...

Immune cells may protect against Alzheimer's

May 19, 2016
Clusters of immune cells in the brain previously associated with Alzheimer's actually protect against the disease by containing the spread of damaging amyloid plaques, a new Yale University School of Medicine study shows.

Blocking inflammation prevents cell death, improves memory in Alzheimer's disease

February 29, 2016
Using a drug compound created to treat cancer, University of California, Irvine neurobiologists have disarmed the brain's response to the distinctive beta-amyloid plaques that are the hallmark of Alzheimer's disease.

Experimental drug shows promise in treating Alzheimer's disease

October 25, 2016
An experimental drug shows promise in treating Alzheimer's disease by preventing inflammation and removing abnormal protein clumps in the brain that are associated with the disease, suggests a study in mice presented at the ...

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

February 23, 2016
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 ...

Recommended for you

Rate of dementia on the decline—but beware of growing numbers

April 17, 2018
The good news? The rate of older Americans with dementia is on the decline.

Research offers potential insight into Alzheimer's disease

April 16, 2018
Slightly elevated beta-amyloid levels in the brain are associated with increased activity in certain brain regions, according to a new study from the Center for Vital Longevity (CVL) at The University of Texas at Dallas.

Americans with a college education live longer without dementia and Alzheimer's

April 16, 2018
Education gives people an edge in their later years, helping them to keep dementia at bay and their memories intact, a new USC-led study has found.

Evidence mounts for Alzheimer's, suicide risks among youth in polluted cities

April 13, 2018
A University of Montana researcher and her collaborators have published a new study that reveals increased risks for Alzheimer's and suicide among children and young adults living in polluted megacities.

Improving brain function in Alzheimer's disease mouse model

April 11, 2018
Using two complementary approaches to reduce the deposits of amyloid-beta in the brain rather than either approach alone improved spatial navigation and memory in a mouse model of Alzheimer's disease. These findings suggest ...

Sleepless nights show ties to Alzheimer's risk

April 10, 2018
Even one night of lost sleep may cause the brain to fill with protein chunks that have long been linked to the development of Alzheimer's disease, a new study warns.

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.