Alzheimer's: How does exercise protect the brain as people age?

Medical News Today

18-06-2025

A new study aims to explain exercise's protective effect on the brain from neurodegenerative diseases like Alzheimer's. Guille eFaingold/Stocksy Past studies show that certain lifestyle changes — such as getting more physical activity — may help lower a person's risk for Alzheimer's disease or slow its progression.
A new study sheds light on how physical activity helps protect the brain from Alzheimer's disease on a cellular level.
Scientists believe these findings may one day lead to new prevention and treatment strategies for Alzheimer's disease.
While there is currently no cure for Alzheimer's disease, past studies show that certain lifestyle changes may help decrease a person's risk for the disease or slow down its progression.
One of these main lifestyle changes is physical activity. A study published in April 2025 reported that increasing physical activity in middle age may help protect the brain from Alzheimer's disease. A study published in May 2025 says older adults who sit less may lower their risk for the condition.
Now, a new study recently published in the journal Nature Neuroscience sheds light on how physical activity helps protect the brain from Alzheimer's disease on a cellular level.
Scientists believe these findings may one day lead to new prevention and treatment strategies for Alzheimer's disease.
'Single-nuclei RNA sequencing (snRNA-seq) is a technique that allows (us to) analyze gene activity by examining the RNA inside on a cell by cell level, giving us precise information about the activation state of each and every single cell in the tissue examined,' Christiane D. Wrann, DVM, PhD, a neuroscientist and leader of the Program in Neuroprotection in Exercise at the Mass General Brigham Heart and Vascular Institute and the McCance Center for Brain Health at Massachusetts General Hospital, and senior author of this study, explained to Medical News Today .
'We used this sophisticated technology to examine how exercise reshapes [the] brain in an important region in the brain of mouse models for Alzheimer's disease,' Wrann added.
Scientists focused on the hippocampus of the brain, which is responsible for making new memories and keeping old ones, as well as processing emotions and learning new information.
Using a mouse model of Alzheimer's disease — that were later verified in human Alzheimer's disease brain tissue samples — researchers found that exercise changed activity in the hippocampus' immune cells called microglia , as well as a specific type of neurovascular-associated astrocyte (NVA) .
NVAs are cells associated with the brain's blood vessels that help make sure the brain receives enough oxygen and is an important part of the blood-brain barrier .
'[Our findings mean] that exercise can remodel these important cell types on the transcriptional/gene expression level, which likely increases their neuroprotective properties. 'It [is] one example, how on the molecular level exercise can improve brain cells in Alzheimer's disease, hopefully rendering them more functionally.'
— Christiane D. Wrann, DVM, PhD
Additionally, Wrann and her team pinpointed a metabolic gene called ATPIF1 as an important regulator to create new neurons in the brain.
'ATPIF1 is a mitochondrial protein that regulates cellular energy production AKA — a gene that regulates energy metabolism,' Wrann detailed. 'Research has shown that stimulating neurogenesis can protect against cognitive decline in aging or Alzheimer's disease. In our study, we show that ATPIF1 is an important regulator of neurogenesis.'
'Exercise is important for your brain health — please keep exercising to protect your brain,' she continued. 'Alzheimer's disease is incurable at the moment. There are smart and dedicated scientists working on finding innovative treatment options.'
'This work not only sheds light on how exercise benefits the brain but also uncovers potential cell-specific targets for future Alzheimer's therapies,' Nathan Tucker, PhD, a biostatistician at SUNY Upstate Medical University and co-senior of the study said in a press release. 'Our study offers a valuable resource for the scientific community investigating Alzheimer's prevention and treatment.'
MNT also had the opportunity to speak with Gary Small, MD, chair of psychiatry at Hackensack University Medical Center in New Jersey, about this study.
Small commented that this study's findings are consistent with the well-documented link between physical activity and brain health, including its role in reducing the risk of Alzheimer's and of slowing its progression in people who already suffer from the disease.
'While the basic conclusion that exercise is important to brain health is not new, these new findings showing the impact of physical activity on key brain cells such as microglia and neurovascular-associated astrocytes provide a more nuanced and deeper understanding why the brain responds to exercise,' he explained.
'Astrocytes and microglia play a crucial role in both initiating and regulating the inflammatory response. Thus, these results further elucidate the link between heightened brain inflammation and cognitive decline,' he said.
'Brain health has a strong influence on our quality of life. Cognitive decline affects not just the physical and behavioral health of the patient, but also has an impact on their caregivers and all who care about the person. The bottom line is that dementia and Alzheimer's disease are not inevitable parts of aging. We can take steps to reduce the risk through lifestyle habits. And even for those who develop the disease, making changes in diet, physical activity, and stress management can slow the progression and extend the time when a person can enjoy a fulfilling quality of life.'
— Gary Small, MD
'The more we understand how cognitive decline occurs, and what can change the course of its development and progression, the more opportunities there are to find ways to treat it,' Small added.