Anticipating Alzheimer’s Before Its Onset
About two-thirds of Alzheimer’s disease (AD) risk is thought to occur due to genetic influences, while about one-third could be influenced by the environment and lifestyle. Researchers are seeking strategies to delay or prevent AD pathophysiological changes. A new study in a mouse model replicating this silent period examines the effects of environmental enrichment on the progression of AD symptoms and pathology.
Early disease stage and behavioral interventions
AD does not begin when symptoms become apparent. Several years of silent development occur before clinical signs emerge. It is crucial to examine AD at the early stages when interventions and mechanisms are most effective. The mouse model contains several human AD-associated mutations in the gene encoding amyloid precursor protein, and mice develop toxic beta-amyloid plaques at six months of age and cognitive decline at 18 months. Therefore, there exists a silent period for several months.
Studies of early pathology
The research group led by Gerd Kempermann, Ph.D., of the German Center for Neurodegenerative Diseases in Dresden, used a mouse model of AD that replicates this silent period. The mice lived in an enriched environment with 60 interconnected cages from the period of six weeks to 23 weeks of age and then transferred to conventional cages after four months. Researchers explored neurogenesis, markers of individualistic behavior, and metabolic patterns in mice living in enriched environments and mice living in ordinary cages.
The benefits of an enriched environment and subsequent results
Living in an enriched environment, including stimulation, physical activities, social engagement, and cognitive challenges, improved several measures of metabolism that are known risk factors for Alzheimer’s disease. For example, enriched living resulted in more significant fluctuations in mice’s blood glucose levels throughout the day. In contrast, mice living in standard cages had a steady blood glucose level that remained constant throughout the day. This prompt change in blood glucose levels demonstrated improved glucose metabolic flexibility, providing further evidence of a beneficial influence on metabolism. Enriched mice also had higher HDL (good) cholesterol and lower triglycerides, indicative of lower heart disease and type 2 diabetes risks.
The effects of enriched living on behavioral changes
Behavioral deficits began early in the course of the disease in the mouse models, according to the research findings. The affected mice had become more similar and rigid, leading to likely deficits very early in the course of the disease. They did not respond appropriately to the offers given to them in the enriched environment.
The effects of enriched living on neurogenesis
The researchers also examined neurogenesis in the mice. The application of the mice had higher rates of neurogenesis than the control mice, classifying the behavior as a failed attempt at compensation. This excess compensation normalized in the enrichment test group. Studies imply that environmental enrichment may reduce the early accumulation of amyloid plaques, indicating a potential strategy to delay symptoms associated with Alzheimer’s disease.
Preventing Alzheimer’s before Identified Symptoms
Alzheimer’s disease is a neurodegenerative disorder marked by cognitive decline and memory loss. Currently, the methods of preventing Alzheimer’s are primarily behavioral, including exercise and maintaining a healthy diet. Aging, genetics, and poor lifestyle factors, such as lack of exercise and sleep, are contributing risk factors for the disease. A recent mouse model study sought to determine whether environmental enrichment on behavior, neurogenesis, and metabolic patterns could create preventive measures for Alzheimer’s disease.
Environmental enrichment in living space
The enriched environment tested by the research group consisted of 60 connected cages containing opportunities for socialization, cognitive challenges, environmental stimulation, and physical activity. Studying the mouse models from six weeks to 23 weeks of age, the enriched mice had more increased fluctuations in blood glucose levels throughout the day. Enriched mice also had increased HDL (good) cholesterol and decreased triglycerides which are both indicative of lower heart disease and type 2 diabetes risk. Human studies done by the National Library of Medicine also found exercise to be beneficial to mental health with a decrease in cognitive performance, oxidative stress, and neuroinflammation.
Memory and Alzheimer’s
Alzheimer’s disease develops over several years of silence before clinical symptoms appear, including memory loss, confusion, and other impairments. Researchers wanted to examine the early stages of Alzheimer’s to find the most effective strategy. The research group used an animal model of Alzheimer’s to study the importance of studying the early stages of the disease when interventions might be most effective. They found that there are already subtle but important behavioral changes even before the first plaques appear, signaling cognitive deficit. The mice developed beta-amyloid plaques at the age of six months, and cognitive decline followed at 18 months, leading to years of silent development in between. For this reason, researchers are searching for ways to determine Alzheimer’s before it emerges fully.
Stimulating neurogenesis
The study by Gerd Kempermann highlighted environmental enrichment’s impact on neurogenesis, indicating that the control mice had lower rates of neurogenesis than the test group cohorts. The research group identified that the mice living in the enriched cages had a higher rate of neurogenesis than those living in the control environment, suggesting that environmental enrichment could provide a preventive strategy strategy in Alzheimer’s disease.
How to improve the preventive measures of Alzheimer’s
Alzheimer’s disease affects more than six million Americans and is the sixth leading cause of death in the United States. The time to stop or slow Alzheimer’s is before it becomes symptomatic, and experts believe environmental enrichment could play a beneficial role. Preventive measures for Alzheimer’s could expand the quality of life and reduce health care costs by delaying the onset of symptoms. Reduced body mass index, better education, vitamin supplementation, and active lifestyle are also potential factors in reducing the risks of Alzheimer’s disease. With the increasing prevalence of the disease, preventative measures and strategies are key to promoting long-term health.
In conclusion, early intervention and prevention could help manage the risks of Alzheimer’s disease. Studies are still uncovering how environmental enrichment and other lifestyle factors contribute to disease prevention, with research reinforcing the importance of maintaining healthy habits throughout life. Alzheimer’s disease is a progressive and debilitating disorder, but with the right research, care, and strategies, we can help alleviate the risks and improve quality of life.
Summary:
The study highlights the importance of studying early stages of Alzheimer’s disease (AD) to establish effective strategies before clinical signs emerge. Results suggest environmental enrichment could be an effective preventive measure, with stimulation of neurogenesis possibly reducing the early accumulation of amyloid plaques. The study underlines early intervention during the phase of silent development when pathology progresses undetected and metabolic changes might hinder the onset of clinical symptoms. Preventive measures such as exercise and maintaining a healthy diet are significant factors as aging, genetics and poor lifestyle factors contribute as risk factors for Alzheimer’s disease. Preventive measures such as reduced body mass index, better education, vitamin supplementation, and action lifestyle could reduce the risks associated with the disease. Although AD is progressive and debilitating, more research can aid in elevated preventive strategies.
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About two-thirds of Alzheimer’s disease (AD) risk is thought to arise from genetic influences, but about one-third could be influenced by environment and lifestyle, opening the door to behavioral interventions that could delay or prevent the pathophysiological changes that occur with AD. Now, a new study in a mouse model of AD examines the effects of environmental enrichment on the progression of AD symptoms and pathology. The study appears in biological psychiatrypublished by Elsevier.
Gerd Kempermann, PhD, of the German Center for Neurodegenerative Diseases in Dresden, Germany, and lead author of the study, stressed the importance of studying the early stages of the disease, when interventions may be most effective.
Dr Kempermann commented: “AD does not start when symptoms become apparent. There is a silent period of decades, during which the pathology progresses undetected. Clinicians and researchers have become increasingly interested in what happens during this phase”.
To study this early pathology, Dr. Kempermann and colleagues used a mouse model of AD that replicates this silent period. The model contains several human AD-associated mutations in the gene encoding amyloid precursor protein (App). These applicationsNL-F mice develop toxic beta-amyloid plaques at 6 months of age and cognitive decline at 18 months.
Dr Kempermann said: “However, we found that there are already subtle but important behavioral changes long before the first plaques appear and cognitive deficits become detectable.”
Mice were housed in an enriched environment, consisting of 60 interconnected cages, from 6 weeks to 23 weeks of age and then transferred to standard cages after 4 months. Living in the enriched environment improved several measures of metabolism, which are known risk factors for AD.
Dr. Kempermann explained: “The [AD model] the mice in our study showed a reduction in individual behaviors. They became more similar and more rigid. As this individualization is largely driven by individual behavior and depends on the plasticity of the brain, we can conclude that the affected mice had behavioral deficits very early in the course of the disease. They did not respond normally to the offers from their environment. This finding is important because it will help us understand how we can better tailor preventive measures during the preclinical phase. It also underscores that prevention must start early.”
The researchers also examined markers of neurogenesis in the mice. Paradoxically, the applicationNL-F the mice had higher rates of neurogenesis than the control mice, which is interpreted as a failed attempt at compensation and paradoxically counterproductive. This excess compensation was normalized by the enrichment exposure.
John Krystal, MD, publisher of biological psychiatrysaid of the work: “This new study suggests that environmental enrichment may reduce the early accumulation of amyloid plaques in a mouse model of AD. This insight may suggest a strategy to delay the development of symptoms associated with this disorder.”
https://www.sciencedaily.com/releases/2023/05/230531150058.htm
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