Monitoring type 2 diabetes may help reduce the risk of Alzheimer’s disease. RichLegg/Getty Images
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Researchers report that evidence suggests there is a relationship between type 2 diabetes and Alzheimer’s disease risk, something that some health professionals call type 3 diabetes.
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They said it’s possible that eating a high-fat diet might lead to higher levels of inflammation, which could increase dementia risk.
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They note that a healthy diet and participating in a healthy lifestyle might reverse the process and decrease the risk of developing Alzheimer’s disease.
There is growing evidence that type 2 diabetes and Alzheimer’s disease are linked, according to research completed at Texas A&M University and presented at the annual meeting of the American Society for Biochemistry and Molecular Biology.
In their findings, which haven’t been published yet in a peer-reviewed journal, researchers examined the relationship between the two diseases, using mice for their experiments.
The scientists said they traced a particular protein in the gut to find out how it influences brain processes. They reported that eating a high-fat diet suppresses a protein called jak3.
The mice without this protein experienced inflammation that began in the intestine and then moved to the liver and the brain. These mice developed Alzheimer’s-like symptoms, including cognitive impairment.
The potential link between Alzheimer’s and type 2 diabetes
The researchers suggest that it could be possible to reduce the risk of Alzheimer’s disease by controlling or avoiding type 2 diabetes.
The scientists note that previous research indicates that diet influences the development and severity of diabetes and, more recently, has been implicated in the risk of developing Alzheimer’s.
demonstrate a 56 percent increased risk for Alzheimer’s disease dementia among individuals with type 2 diabetes,” Narendra Kumar, PhD, the first author of the study and an associate professor of pharmaceutical sciences at Texas A&M, told Medical News Today. “Since there is a known link between diet and lifestyle with type 2 diabetes, we think, yes, diet and lifestyle can be considered as some of the major factors contributing to the progression toward Alzheimer’s disease.”
Although this study has not explored this connection and it is premature to draw any conclusions, Kumar does believe it is possible that this connection would be similar in other types of dementia.
How a leaky gut might be a factor
The researchers at Texas A&M say they have learned that the jak3 protein can lead to a leaky gut, resulting in low-grade chronic inflammation as well as type 2 diabetes, the decreased ability in the brain to clear toxic substances, and dementia-like symptoms.
A leaky gut is a condition in which gaps in the intestinal walls allow toxins and bacteria to leak out of the intestines and into the bloodstream. Not all health professionals recognize this as a distinct medical condition and further research is needed.
The researchers believe that stopping this process, including inflammation, is possible by eating a healthy diet and controlling blood sugar.
Ideally, they said, healthy eating and lifestyle habits can begin early enough to avoid high blood sugar or at least soon enough to reverse prediabetes.
The scientists suggest that these changes can reduce the risk of type 2 diabetes and Alzheimer’s disease.
Connecting type 2 diabetes and Alzheimer’s disease
Around 81% of people living with Alzheimer’s disease also have type 2 diabetes, according to a report by the Keck School of Medicine USC.
The risk of dementia corresponded with the diagnosis of diabetes – the younger the age of developing diabetes, the higher the risk of developing dementia.
Some scientists refer to the link between these two diseases as “type 3 diabetes.”
Because the liver metabolizes food, the researchers say it might be critical to the gut-brain connection.
It is not yet understood why this condition exists, but experts do know that high blood sugar or insulin can harm the brain and increase risk of Alzheimer’s, according to the Alzheimer’s Association.
The brain is the most energy-demanding organ — needing half of all the sugar energy in the body to function correctly. Both high and low blood sugar can damage blood vessels in the brain, according to the Centers for Disease Control and Prevention
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When blood sugar levels are outside of normal range, it can damage nerve and blood vessels in the brain, causing problems with memory, learning, mood, weight gain, and hormonal changes. Over time it can lead to Alzheimer’s disease.
Treating type 2 diabetes
The goal of treatment for type 2 diabetes is to prevent it from causing other health problems, according to the National Institutes of Health
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“Severe obesity is deadly. People’s bodies are 10 to 20 years older than their chronological age. Heart disease is the biggest killer,” said Dr. Mitchell Roslin, the chief of bariatric surgery at Northwell Lenox Hill Hospital in New York who was not involved in the study.
There are several effective treatments, according to Roslin.
“Bariatric surgery is a tool that makes eating less, eating healthier foods, and activity more feasible,” Roslin told Medical News Today. “It is still going to be subject to socioeconomic factors and the environment and stresses people face.”
He added that in the past few years, federal regulators have approved several weight loss medications that can help reduce the risk of diabetes. Tirzepatide (Mounjaro, Zepbound) and semaglutide (Ozempic, Wegovy) work to reduce feelings of hunger and help a person lose weight, which can help control type 2 diabetes.
Diet, exercise, and other lifestyle factors are also important, according to experts.
“Diet and lifestyle changes to address weight is highly effective in reducing your risk for diabetes as well as controlling it,” said Lauren Sepe, a clinical nutritionist at the Kellman Wellness Center in New York who was not involved in the study. “Although the advent of these new and highly effective medications are very helpful to many people, there is a lot of people can do on their own to address their condition.”
“I recommend not only a diet low in carbohydrates and added sugars, but also a diet that addresses inflammation,” Sepe told Medical News Today.
Sepe offered these tips:
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Focus on lean protein, free range protein, wild caught fish, and seafood
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Grass-fed meat in moderation. Grass-fed meat has been shown to contain a higher amount of naturally anti-inflammatory Omega-3 fatty acids, as compared to the conventional meats which are in higher in pro-inflammatory Omega-6 fatty acids
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Healthy fats, such as those found in olive oil, coconut oil, and avocados
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Plenty of non-starchy vegetables as these vegetables tend to be higher in carbohydrate content
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Eggs
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Nuts and seeds, in moderation. They are nutrient dense and contain healthy fats but tend to be higher in calories
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Low sugar fruits in moderation, including apples, citrus fruits, berries, and melons
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Dairy in moderation, preferably good quality, organic versions
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By Eileen Bailey on March 23, 2024 — Fact checked by Kevin Cyr, MD
Latest news
Alzheimer’s may be caused by a build-up of fat in brain cells
hare on PinterestResearch into brain cells is revealing more about the potential causes of Alzheimer’s disease. Luis Alvarez/Getty Images
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Alzheimer’s disease is the most common form of dementia.
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The precise causes of the condition are still being fleshed out.
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For many years, scientists have concentrated on the role of proteins, but this focus is shifting.
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A new study concludes that lipid droplets in specific brain cells may be critical.
Characterized by neurodegeneration and a progressive loss of thinking skills, Alzheimer’s disease still holds many mysteries.
Globally, 55 million people are affected by dementia and by 2050 experts expect this figure to be 139 million.
Despite years of research, the precise mechanisms has been elusive.
A recent study, however, adds another piece to the puzzle.
For the past few decades, scientists have focused on protein build-up in neurons as the lynchpin of Alzheimer’s. So-called plaques and tangles coalesce in neurons and these hallmarks are linked to brain cell death.
Scientists recently designed drugs to clear these proteins, but they are not the silver bullet
that many people hoped for.
More recently, the focus has shifted toward the role of lipid droplets in brain cells.
Alzheimer’s disease and brain cells
A new study
published in the journal Nature examines links between Alzheimer’s risk genes and lipid droplets in microglia, which are immune cells in the brain.
The gene most strongly correlated with risk is the APOE gene. There are various forms of this gene and the one that carries the highest risk
is APOE4.
APOE is involved in lipid processing and in people with Alzheimer’s, the gene’s activity is ramped up
in microglia.
The increased activity by APOE causes lipid droplets to build up within the cells. However, to date, it has been unclear whether this buildup is protective, benign, or harmful.
Details from the study on brain cells and Alzheimer’s
To investigate, the researchers analyzed brain tissue from people who died with Alzheimer’s and a control group who did not have Alzheimer’s.
They measured gene expression within single cells to understand which genes are “turned on.”
Medical News Today spoke with one of the study’s authors, Michael Haney, PhD, an assistant professor in the department of pathology at Perelman School of Medicine at the University of Pennsylvania.
He was surprised that ACSL1, “a key regulator of lipid droplet formation,” was “one of the most upregulated genes in microglia.”
“This is interesting because Alois Alzheimer himself,” who first described the condition, “noted lipid bodies in glia in his patients’ brains over 100 years ago, but this has received little attention,“ Haney explained.
Next, the researchers used a staining technique to see where in the brain these lipid droplet-filled cells were situated.
They said they found that these lipid-containing cells were clustered around protein plaques. This could mean that plaques play a role in lipid accumulation.
To test this theory, the scientists treated microglia with amyloid fibrils, a major component of protein plaques associated with Alzheimer’s.
When they did this, there was a “strong increase” in lipid droplet accumulation, which was particularly pronounced in the presence of APOE4.
New Alzheimer’s research potential
Taken together, the authors believe their study “opens the possibility for a new hypothesis for [lipid droplet]-mediated pathogenesis” in Alzheimer’s.
Speaking with MNT, Haney summarized their results:
“We believe that when microglia encounter the protein buildup common in Alzheimer’s disease, a pro-inflammatory state is triggered in the microglia, which leads to the up-regulation of lipid synthesis enzymes and lipid accumulation in structures known as lipid droplets.”
While lipid accumulation in microglia is a novel finding, scientists have seen this response before. “It also occurs outside the brain when immune cells encounter bacteria,” explained Haney.
“We think a similar state is being triggered in these immune cells of the brain in response to plaques, leading to lipid accumulation and a pro-inflammatory, damaging state for these cells,” he added.
Not a new but an important theory
“This is an important study that highlights the importance of lipid metabolism in Alzheimer’s pathology,” saidAlfred Fonteh, PhD, an associate professor of neuroscience and head of the Biomarker and Neuro-disease Mechanism Lab in the Department of Neurosciences at the Huntington Research Institutes in California.
“With 50 percent of the brain composed of lipids and over 20 years of lipidomic analyses in my lab showing substantial changes in lipid pathways, I am not surprised by these results,” Fonteh, who wasn’t involved in the study, explained to Medical News Today.
Fonteh added that the results of this study confirm what was already known with “the additional detail of a mechanism that can account for the role of lipids in Alzheimer’s.”
Does earlier work on Alzheimer’s support these findings?
Medical News Today also spoke with Hugo Bellen, PhD, and his colleagues from Baylor College of Medicine in Texas. They were not involved in this study, but Bellen’s lab has investigated the molecular basis of neurodegeneration for more than two decades.
They explained that studying postmortem tissue, while interesting and important, may not provide insights into how these conditions begin. The molecular changes that drive Alzheimer’s begin many years, if not decades, before obvious symptoms start.
By the time of death, many years later, unravelling what has happened in the brain is much more challenging.
Bellen’s research
concludes that damaging reactive oxygen species initially buildup because of mitochondrial issues in neurons. These trigger the production of lipids.
These toxic, peroxidated lipids are then transported via APOE to form lipid droplets in glial cells. These lipid droplets promote the breakdown of the peroxidated lipids, which protects the neurons from damage.
They have shown that the Alzheimer’s risk allele, APOE4, is a loss-of-function allele for this lipid transfer process. Loss of APOE — or any of the other proteins required for lipid transport in this pathway — leads to the demise of neurons as the toxic peroxidated lipids build up in the system.
An avenue to new Alzheimer’s treatments?
The authors of the new study hope that focusing on the role of lipid accumulation might help generate new ways to treat Alzheimer’s in the future.
However, there are challenges ahead.
“One of the main challenges in designing drugs to target these lipids or the Alzheimer’s risk genes that transport lipids is that these lipids and lipid-related proteins have important roles outside the brain in processes that you don’t want to disturb,” Haney said.
In other words, he said, we need to find a way to only target lipid accumulation in the right place, and not just lipids in general, because that would cause a range of other difficulties.
However, Haney is hopeful: “I think this might be possible with a better understanding of how this buildup occurs specifically in microglia and what damaging factors they might be secreting.”
Fonteh noted that “[l]ipid metabolism is extraordinarily complex and involves many other enzymes that may be altered in Alzheimer’s.”
“The important aspect of this study is that one size does not fit all,” he said. He expressed the hope that, eventually, we might open the door to more personalized treatment: “The challenge will be teasing out genetics, dietary, and other lifestyle factors when designing drugs.”
Haney also plans to continue this line of work.
“In my new lab, I plan on further characterizing the variety of diseases in which microglia accumulate lipid droplets, how they accumulate these lipids, and how they might damage nearby neurons,” he said.
By Eileen Bailey on March 23, 2024 — Fact checked by Kevin Cyr, MD
