Alzheimer’s disease is the most common form of dementia, affecting more than 5 million adults in the U.S. alone, and more than 55 million
worldwide. Around 1 million people in the U.S. have Parkinson’s disease, with a further 90,000 cases diagnosed each year.
As populations age, the numbers of people with both diseases are predicted to rise. The World Health Organization (WHO) states that by 2050 there will be almost 140 million people
with Alzheimer’s worldwide.
And the number of people with Parkinson’s could rise to 17 million by 2040
.
Both Alzheimer’s disease and Parkinson’s disease are progressive diseases that are, ultimately, fatal. Symptoms of Alzheimer’s disease include memory loss, confusion, cognitive changes, and personality or behavior changes.
Parkinson’s is characterized by tremors, impaired coordination, depression, and other changes in cognitive function.
Currently, both Alzheimer’s disease and Parkinson’s disease are currently incurable, but treatments can help to alleviate symptoms and slow their progress, improving the quality of life of people with the diseases.
Increasingly, research is showing that exercise may also be useful in both delaying onset and slowing the progression of these, and other neurodegenerative diseases. In addition, exercise may be effective as an add-on therapy
alongside current medications.
Dr. Jamie Adams, associate professor in the Department Neurology and the Center for Health and Technology at the University of Rochester Medical Center, NY, told MNT:
“Unfortunately, we do not have any disease-modifying therapies or treatments to prevent or slow the progression of Alzheimer’s disease or Parkinson’s disease. However, there is growing evidence that shows that regular exercise can help slow [the] progression of [the] disease. Regular exercise also has therapeutic and other health benefits.”
“My patients that exercise, feel better and do better,” she added.
Exercise and the brain
“There are numerous studies assessing the link between exercise and reducing the risk of Alzheimer’s and other causes of dementia and it is imperative that this research continues. With every study, we learn more about the disease, which can lead to the development of new treatments,” said Dr. MacSweeney.
But why might exercise help prevent or slow these neurodegenerative diseases? There are several theories.
Inflammation, caused by the overactivity of immune cells — called microglia — in the brain, is a key feature
of both Alzheimer’s disease and Parkinson’s disease.
This inflammation leads to the loss of nerve cells in the brain, with chronic overactivity of microglia
leading to a cumulative loss of neurons.
Exercise can reduce the activity of the microglia cells, which are the immune cells of the nervous system. A 2021 study in older people with Alzheimer’s showed that regular exercise protected cognitive functioning by limiting microglial activity.
Another possible mechanism may be that exercise changes how the brain metabolizes iron. Iron accumulation is associated with the development of beta-amyloid plaques, a characteristic of Alzheimer’s disease.
A study from Finland found that, in mice, regular exercise reduced iron storage in the brain by decreasing levels of a protein called interleukin-6
, which is also linked to inflammation. The mice with lower iron levels also had fewer beta-amyloid plaques.
In Parkinson’s disease, exercise demonstrably reduces the alpha-synuclein clumps that are associated with neurodegeneration.
A study found that irisin, a molecule secreted into the blood during endurance exercise, reduced these clumps, but had no effect on alpha-synuclein monomers that are important for transmitting nerve impulses
.
Physical activity has also been shown to increase levels of two other important chemicals, as Dr. MacSweeney explained :
“Exercise stimulates the production of chemicals such as BDNF (brain-derived neurotrophic factor) and IGF (insulin growth factor) These help to stimulate new cell growth in certain areas of the brain and strengthen connections.”
Studies have shown that BDNF
, administered externally, or produced via increased physical activity, may be useful as part of a therapeutic regime for Parkinson’s disease.
And the therapeutic use of IGF has been proposed for many disorders of the nervous system, including Alzheimer’s disease, Parkinson’s disease, amyotrophic lateral sclerosis (ALS, or motor neuron disease), and multiple sclerosis (MS).
“Exercise is thought to encourage brain cell growth and survival, which may help reduce the risk of developing dementia. Studies have also shown that exercise increases the size of the brain structure linked to memory and learning.”
– Dr. Emer MacSweeney
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About 32 million people globally have Alzheimer’s disease.
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Researchers continue to look for a way to stop or slow disease progression.
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Researchers from the Icahn School of Medicine at Mount Sinai found that changing certain cellular interactions helps clear out beta-amyloid plaques from the brain, considered a sign of Alzheimer’s disease.
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Scientists believe these findings may lead to new treatment options for the condition.
Researchers continue to look for a way to stop or slow the progression of Alzheimer’s disease — a type of dementia affecting about 32 million people
around the world.
One such team of researchers hails from the Icahn School of Medicine at Mount Sinai in New York. In their new study published in the journal Nature Neuroscience
Trusted Sour, researchers found that changing certain cellular interactions helps clear out beta-amyloid plaques
from the brain, considered a sign of Alzheimer’s disease.
Medical News Today spoke to the three senior authors of the study about its findings: Roland H. Friedel, PhD, who is an associate professor of neuroscience and neurosurgery at Icahn, Hongyan Zou, MD, PhD, a professor of neurosurgery and neuroscience at this institution, and Bin Zhang, PhD, who is professor of genetics and genomic sciences at Icahn.
“Alzheimer’s disease remains a medical challenge as currently effective treatment is still not available,” the study authors pointed out.
“Amyloid plaque is a pathological hallmark of Alzheimer’s disease and plaque burden positively correlates with disease severity. Amyloid plaques are neurotoxic
— finding ways to help clear out plaques will help reduce neurotoxicity and attenuate neuroinflammation,” they told us.
Plexin-B1: A key player in Alzheimer’s?
For this study, researchers focused on a protein called plexin-B1
.
“Plexin-B1 is a membrane receptor, originally identified as an axon guidance (molecule) important for axon wiring during neurodevelopment,” the study authors explained to MNT.
“Recent big data analysis by Dr. Bin Zhang’s system biology group computationally identified plexin-B1 as a hub gene underlying late-onset Alzheimer’s disease,” they told us.
“This project showcases a team approach from three different labs — hence three senior authors — to tackle the function of plexin-B1 in Alzheimer’s disease for the first time,” noted the study authors.
Removing plexin-B1 could clear amyloid plaque
The scientists looked at how plexin-B1 protein interacted with reactive astrocytes
— cells in the central nervous system, including the brain, that activate in response to disease or injury.
The senior authors explained that:
“Astrocytes are a type of glial cells that support neuronal function. Reactive astrocytes react to Alzheimer’s disease by surrounding the amyloid plaques, forming a structure called [a] glial net
.”
“Our study found that plexin-B1 activation in reactive astrocytes prevents them from [properly functioning] to clear plaques,” they continued. “Removing plexin-B1 can reverse this, leading to better amyloid clearance and smaller plaque burden.”
Finding new ways to target plexin-B1
All three researchers are currently working to find therapeutic ways to target plexin-B1. Zhang’s team is reportedly trying to identify candidate drugs using artificial intelligence
(AI)-aided approaches. And Zou and Friedel’s labs are teaming up to generate function-blocking antibodies against plexin-B1.
“The three teams will work together to identify effective drugs or antibodies to modulate plexin-B1 function in reactive astrocytes,” the study authors said. “We believe our research will contribute significantly to the global effort to combat Alzheimer’s disease.”
“This study not only confirms one of the most important predictions from our gene network models but also significantly advances our understanding of Alzheimer’s. It lays a solid foundation for developing novel therapeutics targeting such highly predictive network models,” they argued.
“Our study opens new pathways for Alzheimer’s research, emphasizing the importance of cellular interactions in developing neurodegenerative disease treatments.”
– Roland H. Friedel, PhD; Hongyan Zou, MD, PhD; Bin Zhang, PhD
Potential for new Alzheimer’s treatment
After reviewing this study, Karen D. Sullivan, PhD, ABPP, a board-certified neuropsychologist, owner of I CARE FOR YOUR BRAIN, and Reid Healthcare Transformation Fellow at FirstHealth of the Carolinas in Pinehurst, NC, who was not involved in the research, told MNT this innovative study offers a new window of hope for Alzheimer’s disease treatment.
“With so many therapeutics focusing on beta-amyloid, this evidence suggests that by relaxing the spacing of the ‘connector cells’, i.e., glia
, we may be able to reduce neuroinflammation and help the pathological plaques of Alzheimer’s disease to be more compact,” Sullivan continued. “In turn, this is expected to reduce the number of neurons that get consumed by the disease i.e., less cell death.”
However, the research is still at an early, preclinical stage, she cautioned.
“This study was done in a genetic mouse model of Alzheimer’s disease,” noted Sullivan. “We always want [to] see results like this translate well into the human brain before we get too hopeful that a new drug can be developed from this discovery.”
Is focusing on removing amyloid plaque buildup the way to go?
MNT also spoke with Clifford Segil, DO, a neurologist at Providence Saint John’s Health Center in Santa Monica, CA, about this study. Segil was also not involved in this research.
Segil expressed more doubt about the therapeutic potential tied to this study’s findings. In his view, targeting plaque build-up in the brain may not necessarily be the best way to go in fighting Alzheimer’s.
Without mincing words, he said: “It upsets me to see researchers blindly note cognitive decline and memory loss from neurodegeneration are linked to amyloid-beta and neurofibrillary tangles, when clinicians on the front line treating and diagnosing patients with dementias continue to sour on the ‘amyloid hypothesis’ as clinically-available and highly-effective anti-brain-amyloid medications continue to produce modest improvements in cognition per pharmaceutical company provided data and without any noticeable clinical improvements to [a] clinical neurologist.”
Referencing the recent controversy that cast a shadow of doubt over the widely-embraced hypothesis that beta-amyloid plaques are at least partly to brain for Alzheimer’s symptoms, Segil pointed out that:
“This paper’s claim [that] amyloid and tangles cause cognitive decline and memory loss is becoming less believable over time as anti-brain amyloid medications are being used and patients receiving these medications in the real world are not having any noticeable improvements.”
He also noted that many clinicians like himself see patients with high brain-amyloid burden without any cognitive complaints, as well as those with low brain-amyloid burden and disabling and severe cognitive complaints.
“Findings focusing on removing amyloid plaque buildup are not going to help find new ways to treat the memory loss patients with Alzheimer’s dementia get,” Segil claimed.
Nevertheless, he met some of the other study findings with more enthusiasm, saying: “I am excited to see if the plexin-B1 noted in this study that works on brain neuron support cells or glia can produce improvements in memory separate [from] their effects on brain amyloid.”
“I would like more research done on brain microglia and [the] brain lymphatic system
,” Segil added. “When I obtained my [Bachelor of Science] in neuroscience in 1996, there was no agreement then [that the] brain had a lymphatic system, and more research should be done on novel ways to engage brain microglial cell function as they relate to memory loss,” he told us.
— the active ingredient in glucagon-like peptide-1 (GLP-1) receptor agonist medications Ozempic and Wegovy — may help reduce the progression of kidney disease in people with type 2 diabetes.
Now, research recently presented at the 61st European Renal Association Conference in Stockholm, Sweden, reports semaglutide may also help protect kidney function in people who have overweight or obesity and also have established cardiovascular disease.
The research has not yet been published in a peer-reviewed journal.
Semaglutide use lowers risk of adverse kidney-related events
This study’s results are from the SELECT
(Semaglutide Effects on Heart Disease and Stroke in Patients with Overweight or Obesity) trial, which includes more than 17,000 participants.
After an average follow-up of about 3.5 years, scientists discovered that adverse kidney-related events — such as a significant decline in kidney function, death from kidney causes, or onset of persistent macroalbuminuria — were experienced by 22% fewer participants in the group receiving semaglutide injections compared to the placebo group.
“By addressing key markers of kidney health, semaglutide 2.4 mg [milligrams] weekly may contribute to a significant reduction in the risk of kidney-related complications, including chronic kidney disease and end-stage renal disease,” said Prof. Helen M. Colhoun, MD, the AXA Chair in Medical Informatics and Life Course Epidemiology at the University of Edinburgh in Scotland, United Kingdom, and lead author of this study, in a press release.
“This could lead to improved management of comorbidities and, ultimately, enhance the quality of life for individuals with obesity,” she suggested.
Improved eGFR, UACR measurements with semaglutide use
Researchers examined how semaglutide might impact a person’s estimated glomerular filtration rate (eGFR), which measures how much waste and excess water the kidneys filter out of the blood through urine.
Participants receiving semaglutide had a significantly lower decline in eGFR than those in the placebo group, indicating semaglutide’s potential kidney function protection in people with pre-existing kidney impairment.
The scientists also looked at how semaglutide affected participants’ urinary albumin-to-creatinine ratio (UACR)
. UACR measures the ratio of the protein albumin
to waste product creatinine in the urine, which helps doctors determine if a person has albuminuria, which can be a sign of kidney issues.
In participants using semaglutide, compared to baseline measurements researchers reported an average 8.1% decrease in UACR with those with normal albumin levels, a 27.2% decrease in those with microalbuminuria, and a 31.4% decrease in those with macroalbuminuria compared to those receiving the placebo.
“The observed benefits in eGFR and UACR are particularly encouraging, suggesting potential for the enhanced management of kidney complications in the patient population with overweight and obesity without diabetes,” Colhoun said in the press release.
“The findings also underscore the importance of continued research into the possible renal benefits of semaglutide and highlight its role as a promising therapeutic option in the multifaceted management of cardiovascular and renal health in this high-risk population,” she added.
Why does obesity negatively impact the kidneys?
Mir Ali, MD, bariatric surgeon and medical director of MemorialCare Surgical Weight Loss Center at Orange Coast Medical Center in Fountain Valley, CA — who was not involved in this study — told Medical News Today this study’s findings were not surprising.
“We’ve found with any kind of weight loss — whether it’s from the medications, surgical, or just even diet and exercise — all organ functions seem to improve in people who are significantly overweight. So the fact that kidney function is protected and improved with weight loss is good that it be documented, but it’s not surprising to me.”
– Mir Ali, MD
Ali explained that when somebody is significantly overweight or obese, they’re stressing all their organs including the kidneys, heart, lungs, and liver.
“All their organs are working less efficiently, having to work harder, because they have to process more things through the body,” he continued.
“So when you lose weight, it takes that extra stress off the organ. There’s also a significant component of inflammation
that occurs with obesity, and that inflammation can affect the kidneys, heart, [and] lungs,” Ali detailed.
How cardiovascular disease can harm kidney function
MNT also spoke with Cheng-Han Chen, MD, a board-certified interventional cardiologist and medical director of the Structural Heart Program at MemorialCare Saddleback Medical Center in Laguna Hills, CA — who was also not involved in this study — about why cardiovascular disease could negatively impact kidney function.
“A lot of kidney function itself depends on the heart function as the kidneys’ job is to filter blood, and its efficacy depends on how well the blood is sent to the kidney from the cells,” Chen explained.
“In addition, many of the disease processes in cardiovascular disease, such as atherosclerosis, can also affect the blood vessels in the kidney,” he pointed out.
“Furthermore, the kidneys function themselves conversely from heart function, as some of the function of the kidneys is to regulate blood vessel dilation and constriction,” Chen added. “And so this hypotension also affects the health of blood vessels of the heart.”
More methods of protecting kidney function needed
Chen said it is important for researchers to continue to find new ways of protecting kidney function in people who are obese with heart disease because kidney disease has significant morbidity and mortality in the United States
.
“So any treatments we have to slow the progression of kidney disease have the potential to benefit a large portion of the American population,” he continued.
“It is encouraging to see that semaglutide — an important medication that has been shown to be beneficial in patients with diabetes, as well as patients with obesity — has the capability of slowing [the] progression of kidney disease as well,” commented Chen.
“Future longer-term research [should] look to see if this benefit to kidney function will extend out to prevent poor kidney outcomes such as initiation of dialysis or even kidney transplant,” he advised.
Ali said that through future research, it would be interesting to see if this improvement in kidney function through the use of semaglutide is independent of weight loss.
“There was a recent study looking at cardiovascular health and they found that semaglutide improves cardiovascular health, independent of weight loss
,” he told us. “So even if patients didn’t lose a lot of weight, their cardiovascular health improved with [the] use of semaglutide.”
“The theory is it has a reduction in inflammation, so it would be interesting to see if that’s also true for the kidneys — is that improvement in kidney function or protection of the kidneys independent of the weight loss or is it directly related to the weight loss?” Ali added.
