Stem cells improve memory, reduce inflammation in Alzheimer’s mouse brains

Investigators hope to advance the research to larger animals

10:45 AM

Author | Noah Fromson

Xray of a stem cell in a mouse brain.
Human neural stem cells were engineered to express green fluorescent protein, then injected into the memory centers of the Alzheimer’s disease mouse brain. The stem cells (green color) are at the site of injection and also traveling through various areas of the brain (background of blue stained cells). Credit: Michigan Medicine

When people think of Alzheimer’s Disease and possible treatment, amyloid — and the accumulation of plaques that invade the cerebral cortex — is often brought up first.  

However, scientists are finding that Alzheimer’s is influenced by many factors, including neuroinflammation and disrupted metabolism. 

By transplanting human neural stem cells, researchers led by Michigan Medicine improved memory and reduced neuroinflammation in a mouse model of Alzheimer’s Disease, suggesting another avenue for potential treatment. 

The results are published in Frontiers in Aging Neuroscience.  

“The beneficial effects of transplanting human neural stem cells within the brains of Alzheimer's Disease mice occurred despite amyloid plaque levels remaining unchanged, which lends further evidence that strategies targeting neuroinflammation may be a promising therapeutic strategy, independent of amyloid plaques,” said lead author Kevin Chen, M.D., clinical assistant professor of neurosurgery and neurology at Michigan Medicine.

“Additionally, the treatment was associated with normalized inflammation in the microglia, which are the innate immune cells of the brain that become activated with Alzheimer’s Disease. As the disease progresses, microglia and their inflammatory signaling is thought to contribute to neuron loss.”

A team at Michigan Medicine’s NeuroNetwork for Emerging Therapies transplanted neural stem cells into the memory centers of transgenic mice that expressed mutations associated with familial Alzheimer’s Disease. They had both the test mice and control mice perform a task called the Morris water maze to assess spatial memory and learning eight weeks after transplant. 

Investigators found that Alzheimer’s disease mice transplanted with stem cells had their learning curves restored to resemble the control mice with normal learning and memory.

Additional testing through spatial transcriptomics — a method to measure gene expression in areas across the brain— revealed over 1,000 differently expressed genes that were normalized in the memory centers of the Alzheimer’s Disease mice after transplantation. 

In analyzing the gene expression changes specifically in microglia, the genetic markers linked to progression of Alzheimer’s Disease were also restored to levels close to control mice. This suggested a reduction in neuroinflammation and disease progression. 

Researchers say the improvements reported after stem cell transplantation must be further studied in mice before advancing to larger animals and, eventually, humans. 

“Our research is incredibly important and continues to support the promise of stem cell therapies in neurodegenerative diseases,” according to senior author Eva Feldman, M.D., Ph.D., director of the ALS Center of Excellence at U-M and James W. Albers Distinguished University Professor at U-M.

“These preclinical studies are the required first step on the road to stem cell therapies.”

Additional authors: Include Mohamed H. Noureldein, Ph.D., Lisa M. McGinley, Ph.D., John M. Hayes, Diana M. Rigan, Jacquelin F. Kwentus, Shayna N. Mason, Faye E. Mendelson, all of University of Michigan, and Masha G. Savelieff, CRED, of University of North Dakota. 

Funding: This research was supported by the National Institutes of Health, The Handleman Emerging Scholar Program, the NeuroNetwork for Emerging Therapies, The Robert E. Nederlander Sr. Program for Alzheimer’s Research, the Sinai Medical Staff Foundation and an Alzheimer's Association grant.

Michigan Research Core: Advanced Genomics Core

Citation: “Human neural stem cells restore spatial memory in a transgenic Alzheimer’s disease mouse model by an immunomodulating mechanism,” Frontiers in Aging Neuroscience. DOI: 10.3389/fnagi.2023.1306004 

Sign up for Health Lab newsletters today. Get medical tips from top experts and learn about new scientific discoveries every week by subscribing to Health Lab’s two newsletters, Health & Wellness and Research & Innovation.

Sign up for the Health Lab Podcast: Add us on SpotifyApple Podcasts or wherever you get you listen to your favorite shows.

More Articles About: Lab Report Neurosurgery & Neurological Procedures Neurological (Brain) Conditions Basic Science and Laboratory Research All Research Topics
Health Lab word mark overlaying blue cells
Health Lab

Explore a variety of health care news & stories by visiting the Health Lab home page for more articles.

Media Contact Public Relations

Department of Communication at Michigan Medicine

[email protected]


brain stem blue green slice
Health Lab
Monoclonal antibodies preserve stem cells in mouse brains, bring promise for future studies
Using antibodies instead of traditional drugs, stem cells last significantly longer when used in pre-clinical animal models.
Stay Informed

Want top health & research news weekly? Sign up for Health Lab’s newsletters today!

Featured News & Stories brain stem blue green slice
Health Lab
Monoclonal antibodies preserve stem cells in mouse brains, bring promise for future studies
Using antibodies instead of traditional drugs, stem cells last significantly longer when used in pre-clinical animal models.
green background connecting to teal skull with brain inside both just outlines made out of felt
Health Lab
Can preventing inflammation improve heart and brain health?
Michigan Medicine research study aims to address inflammation’s role in diseases of the heart and brain.
graphic drawn mouse snoozing in purple background and pink maze around it breathing while sleeping and see pink brain inside head with white sparkles fading in and out
Health Lab
Studies uncover the critical role of sleep in the formation of memories
Two new studies from University of Michigan reveal what's happening inside the brain during sleep and sleep deprivation to help or harm the formation of memories.
Lab of Erin M. Janssen, M.D., Ph.D.
Medical School News
Labs go platinum: Research teams record efforts to achieve sustainability certification
Many Michigan Medicine labs are taking time to ensure that they are doing their part to support the Medical School’s major initiatives, including the push for carbon neutrality.
cancer cell blue yellow
Health Lab
Accessibility issues in cancer care
Researchers at the University of Michigan are finding that many patients may be encountering significant barriers to cancer care, even from their first phone call to a clinic.
stethoscope blue yellow
Health Lab
New drug could help those with CAH reduce the use of corticosteroids
Michigan Medicine researchers discover that a new drug could help those with CAH, or congenital adrenal hyperplasia, reduce the use of corticosteroids.