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The identification of biomarkers for Alzheimer’s or Parkinson’s disease that can be found in bodily fluids like blood, urine, and saliva could aid in the discovery and development of new medications and therapies. Last year, a team of scientists created a wireless gadget that can identify SARS-CoV-2 strains in particular by detecting a very small number of molecules. They have now demonstrated that their gadget can be modified to identify chemicals connected to Parkinson’s and Alzheimer’s diseases. Researchers from the University of California, San Diego have demonstrated that their wireless, handheld device, which they developed to identify particular biomolecules, can also identify molecules linked to Parkinson’s and Alzheimer’s diseases. Initially, the instrument was designed to identify SARS-CoV-2, the virus responsible for COVID-19. Aptamers, which are brief strands of DNA or RNA that bind exclusively to particular molecules, are how it functions. Electrical energy can flow when binding occurs on the machine’s single-atom-thick graphene layer, producing a positive reading that verifies the presence of the molecule. In a previous study, it was demonstrated that their device could identify particular strains of the SARS-CoV-2 virus when very few viruses were present.

In their most recent study, this group of researchers demonstrated that their apparatus can identify various forms of tau and beta-amyloid, peptides that are characteristic of Alzheimer’s disease, as well as α-synuclein, a peptide that is present in higher concentrations in the brains of patients with Parkinson’s disease. To test the device’s capacity to identify these molecules, samples extracted from the autopsied brains of departed patients were used. The quantity of Americans who suffer from Alzheimer’s disease. S. may increase from 6.77 million to 13.78 million by 2060 if no major advancements are made in the field. While it has proven difficult to design clinical trials demonstrating the efficacy of drugs with cohorts of patients already exhibiting symptoms of the disease, breakthroughs are required not only in the diagnosis but also in the development of treatments. Currently, MRI, PET scanning, and neurocognitive testing are used in combination to detect Alzheimer’s disease, often after cognitive decline and other symptoms have started. The way that PET scans function is by looking for amyloid plaques, which are created when a peptide called beta-amyloid tangles with tau to form plaques. The cognitive decline that is observed in patients with Alzheimer’s disease is believed to be caused by these tangles interfering with nerve cell signaling in the brain.

The majority of studies concentrate on the existence, functions, and potential mechanisms of these peptides because Alzheimer’s disease patients’ brains have these plaques. Because these peptides are found in the brain, isolating them is still difficult and may require surgery. The findings of the study demonstrated that the apparatus the researchers had created could accurately and precisely identify several forms of these beta-amyloid peptides at low concentrations. Lead author Dr. Ratnesh Lal told Medical News Today in an interview, “What we saw in this paper is that the amount of beta-amyloid that goes into the brain in the saliva is almost 1,000 times more than what is the sensitivity of our system.”. He claimed that because there was no cross-reactivity to skew results, the device’s strength came from the electrical system’s sensitivity.

According to the paper’s authors, they plan to test the device’s ability to identify these molecules in blood plasma and cerebrospinal fluid before moving on to saliva and urine. Dr. Thomas K. Karikari, an assistant professor of psychiatry at the University of Pittsburgh who studies biomarkers for Alzheimer’s disease and was not involved in the research, stated that more research needs to be done to determine the best kind of biomarkers to detect Alzheimer’s disease in various types of body fluid. Standardized pathology tests on tau and amyloid present additional difficulties in obtaining consistent enough results to prevent false positives and negatives. Because amyloid is naturally very sticky, it can be challenging to separate and manipulate. Because of the blood-brain barrier, blood concentrations and concentrations in other tissues outside of the brain may not always reflect most changes observed in the brain. Dr. Karikari told  that his own research had looked at the phosphorylation patterns on Alzheimer’s specific tau-peptides to determine which specific molecules could be determined to have come from the brain and present in different concentrations in Alzheimer’s patients compared to a non-disease population. Put another way, you cannot tell if these biomarkers have come from the brain and not somewhere else in the body.

His earlier studies have demonstrated that tau binding is especially strong in the vicinity of the salivary gland. At the time, we demonstrated that there was no difference in saliva quality between the diagnostic group. Because tau in saliva would not always come from the brain, it was determined that tau in saliva was not a reliable biomarker for Alzheimer’s disease. “So we actually ended that at that point,” Dr. Karikari said. But now, he stated, “perhaps we can go back and be able to characterize the tau from the saliva much better,” since research has been done to identify the phosphorylation patterns on tau that define Alzheimer’s disease. “Dr. Less research has been done on urine, according to Karikari, and gathering urine from elderly patients who are incontinent presents unique difficulties. The device should be on the market in a year, according to the paper’s authors, who say they intend to apply for FDA approval in the next five to six months.

REFERENCES:

https://www.medicalnewstoday.com/articles/wireless-handheld-device-may-detect-alzheimers-parkinsons-biomarkers-early
https://newatlas.com/medical/portable-device-alzheimers-parkinsons-biomarkers/
https://www.altonmemorialhospital.org/Health-Library/View-Content?contentTypeId=6&contentId=2118881603
https://challenge.carleton.ca/parkinsons-alzheimers-early-detection/

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It has been discovered that higher concentrations of proteins that impair brain function are linked to visceral fat in the abdomen. According to researchers, creating metrics for visceral fat may help identify Alzheimer’s disease early on. According to experts, losing belly fat may help reduce the chance of getting Alzheimer’s. Adults in their middle years who have visceral fat around their internal organs in their abdomen may be more susceptible to Alzheimer’s. Based on research presented at the annual meeting of the Radiological Society of North America, having such fat deposits could cause changes in the brain related to Alzheimer’s up to 15 years before symptoms of the neurological disease appear — and as early as age 50. In this study, middle-aged people without any indications of cognitive problems were asked to participate in order to find correlations between high body mass index (BMI) scores, obesity, insulin resistance, and fatty abdominal tissue and amyloid and tau proteins, which are known to disrupt cellular communication in the brain.

Researchers at Washington University School of Medicine in St. Louis were led by Dr. Mahsa Dolatshahi, a post-doctoral research fellow at the Mallinckrodt Institute of Radiology (MIR). Louis, the brain region known to be affected early by amyloid pathology in Alzheimer’s disease, previously reported that a higher visceral to subcutaneous fat ratio in the belly was associated with a higher presence of amyloids in the precuneus cortex. According to those researchers, there was a correlation between elevated brain inflammation and higher levels of visceral fat. According to the new study, men are more likely than women to have belly fat and Alzheimer’s diseaseNo previous study has linked a specific type of fat to the actual Alzheimer’s disease protein in cognitively normal people, despite other studies linking BMI with brain atrophy or even a higher dementia risk, Dolatshahi stated in a press release. Comparable research has not looked into the distinct roles of visceral and subcutaneous fat, particularly in relation to the amyloid pathology of Alzheimer’s disease, as early as midlife. Dr. Mary Ellen Koran, an assistant professor of radiology and radiological sciences at Vanderbilt University Medical Center, said, It makes sense that visceral fat is linked to poorer brain health since we already know it’s linked to so many bad health outcomes, including heart health. But it’s important that we do the studies like these to define that link with evidence..

Visceral fat’s inflammatory secretions may lead to inflammation in the brain, one of the main mechanisms contributing to Alzheimer’s disease, according to DolatshahiWe don’t know whether this is a cause or effect—possibly an unhealthy lifestyle is linked to worse brain health in addition to more visceral fat, said Koran, a radiology expert who has identified Alzheimer’s disease. Before we can advance this clinically, more research in this area is necessary. For instance, she stated, It needs to be investigated because I don’t think we know what a ‘normal’ amount of visceral fat is. The results, according to researchers, may make it possible to identify Alzheimer’s disease early in an at-risk groupWe now have a uniquely better understanding of why this factor may increase risk for Alzheimer’s disease by moving beyond body mass index (BMI) in better characterizing the anatomical distribution of body fat on MRI, stated Dr. Cyrus Raji, senior study author, associate professor of radiology and neurology, and director of neuromagnetic resonance imaging at MIR.

According to Koran, the issue with utilizing BMI to evaluate health risks is that it ignores people who have a lot of muscle mass. Similarly, visceral and subcutaneous fat cannot be distinguished using waist circumference as a benchmark. Since visceral fat is known to be associated with a number of negative health outcomes, the expert suggested that alternative methods of assessing visceral fat be explored. Non-invasive imaging is a good fit for this purpose. Maybe in the future, we’ll be able to measure this using an inexpensive, radiation-free technique like ultrasound. According to the study, reducing belly fat may lower the risk of Alzheimer’s. According to Taylor Wilson, founder of Active Recovery Companions and an expert in nutrition and exercise, one strategy that has been proven effective in reducing belly fat is engaging in regular aerobic exercise, which includes activities like running, swimming, cycling, and dancing. These activities raise your heart rate and increase oxygen flow throughout your body. He told Medical News Today, Your body burns calories when you engage in aerobic exercise, including those stored in the belly area.Over time, a decrease in belly fat and overall weight loss may result from this calorie burn. Furthermore, studies have demonstrated that aerobic exercise significantly reduces belly fat in comparison to resistance training alone.

We know we can target fat with exercise and a healthy diet, but there are also new, effective drugs like Ozempic coming to market, Koran continued. However, more research is needed to determine how these medications affect visceral fat and brain function over the long run. Although the Food and Drug Administration has approved Ozempic and other comparable drugs for the treatment of type 2 diabetes, most of them still lack the necessary approval to be used for weight loss. Currently, some doctors are prescribing some of those medications off-label to help patients lose weight.

REFERENCES:

https://www.medicalnewstoday.com/articles/hidden-belly-fat-in-midlife-linked-to-alzheimers-disease
https://www.insideprecisionmedicine.com/topics/patient-care/hidden-belly-fat-linked-to-higher-alzheimers-risk/
https://neurosciencenews.com/midlife-visceral-fat-alzheimers-25235/
https://www.healthline.com/health-news/this-type-of-hidden-belly-fat-linked-to-higher-alzheimers-disease-risk

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Small blood vessel models are being grown in a lab to help researchers investigate the possible causes of cerebral small vessel disease. They stated that they hope to find viable treatments for the ailment, which can affect patients with type 2 diabetes and high blood pressure. Although the results are encouraging, experts warn that there is still much work to be done in this area of study. In order to determine what causes small blood vessel-like models to leak in people with specific medical conditions that raise the risk of vascular dementia and stroke, scientists at Cambridge University in England have grown the models in a lab. The journal Stem Cell Reports published the study’s findings today.

Small vessel disease (SVD) of the brain primarily occurs in two forms. The most prevalent usually affects people in their middle years and is linked to type 2 diabetes and elevated blood pressure. People in their mid-30s are typically found with the other rare form, which is inherited. A COL4 gene mutation is one of the causes. Researchers at Cambridge’s Victor Philip Dahdaleh Heart and Lung Research Institute used skin samples from patients suffering from a rare form of SVD brought on by COL4 gene mutations. Induced pluripotent stem cells, which can differentiate into nearly any type of cell in the body, were produced using these. By using these cells to create new cells, the researchers were able to model the disease that affects the brain vessels. The complex support system that surrounds cells, known as the extracellular matrix, was disrupted by the mutations in this particular form of SVD, according to the scientists. Tight junctions were especially affected by this disruption, which made the blood vessels leaky. The overproduction of molecules known as matrix metalloproteinases (MMPs), which are required to preserve the extracellular matrix’s structure, was also linked to the disturbance that the researchers saw. The group used medications that block MMPs to treat the cells. To do this, they employed the anti-cancer medication marimastat, the antibiotic doxycycline, or both. According to the researchers, blocking the MMPs with medication halted the leak and undid the harm. They did point out that these medications can have harmful side effects.

SVD patients are routinely treated by Dr. Sean Savitz, a professor and the director of the Institute for Stroke and Cerebrovascular Diseases at UTHealth Houston. He expressed his admiration for the study’s conclusions to Medical News Today, but he issued a warning, noting that the researchers only examined rare genetic mutation cases. This is a very well-done study that raises some interesting questions about the biological and molecular alterations that may be underlying some of the pathologies observed in brains affected by small vessel disease (SVD). Not involved in the study, Savitz stated, SVD is very common, especially in older patients with vascular risk factors. He continued, It’s very interesting to use skin cells to recapitulate the conditions in small vessel disease. The fact that a common antibiotic could undo some of the changes seen was intriguing. But we must remember that the patients from whom the cells were taken had uncommon genetic mutations.

According to the researchers, approximately half (45%) of dementia cases globally and roughly one-fifth of ischemic strokes are caused by SVD. These happen when the brain’s blood and oxygen supply are cut off by a blood clot. They represent the most prevalent kind of stroke. According to an article published in Advances in Clinical and Experimental Medicine, cerebral small vessel disease is the most prevalent, progressive, and chronic type of vascular disease. It impacts the capillaries, arterioles, and tiny veins that supply the brain’s deep structures, including the white matter. According to Dr. Shae Datta, director of cognitive neurology at NYU Langone Hospital—Long Island and co-director of NYU Langone’s Concussion Center in New York, SVD causes cognitive impairment, ischemic or hemorrhagic stroke, problems with mobility, and neuropsychiatric symptoms. Datta, who was not involved in the study, told Medical News Today that regular exercise, healthy diet, Mediterranean diet, folic acid, and vitamin B12 and avoiding adverse lifestyle factors like smoking, excess alcohol, or high dietary sodium, are all associated with having fewer SVD features in observational studies.

According to Dr. Catherine Arnold, a neurologist at Northwell Lenox Hill in New York who was not involved in the study, there are typically multiple coexisting conditions with SVD. These may obstruct the course of therapy. In an interview with Medical News Today, Arnold stated, The results of this study allow a better understanding of some of the potential mechanisms behind the development of small vessel disease (SVD) and potential mechanisms for future treatments. However, this study alone does not provide enough clarity or insight to change practice entirely, given the likelihood of multiple co-existing processes that contribute to the disease, the speaker continued. Future research is necessary to determine whether the findings hold true for the majority of patients with cerebral small vessel disease who also have vascular risk factors like diabetes and hypertension, according to Savitz. Therefore, the results of these experiments cannot be immediately applied to a clinical setting; however, the study lays the groundwork for particular future treatment development directions. Other than vascular risk factor modifications, which include blood pressure, glucose, cholesterol, and adherence to a healthy diet, we do not currently have any specific treatments.

Treating the underlying cause of a condition, such as an ischemic stroke, is often the first step in treatment. According to Morales, secondary prevention strategies often involve the use of statins, glycemic control, antihypertensives, antithrombotics, and other medications in addition to encouraging social interaction, a Mediterranean diet, and frequent exercise. Medication side effects can contribute to compliance issues, which can arise frequently. Is it effective? Evidence suggests that some of the effects and progression of vascular disease can be mitigated by our current strategies; however, more effective precision-based medical strategies that target these mechanistic pathways are clearly needed.

REFERENCES:

https://www.medicalnewstoday.com/articles/how-research-into-small-blood-vessels-may-help-prevent-stroke-vascular-dementia
https://www.port.ac.uk/news-events-and-blogs/news/tiny-blood-vessels-in-brain-could-be-key-to-treating-vascular-dementia
https://www.cam.ac.uk/research/news/lab-grown-small-blood-vessels-point-to-potential-treatment-for-major-cause-of-stroke-and-vascular

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The study, which was written up in the journal Current Biology, employed a computational model to delve deeper into the complexities of navigational errors that have already been linked to Alzheimer’s disease. Participants were divided into three groups by researchers, under the direction of Professor Neil Burgess and colleagues in the Space and Memory group* at the UCL Institute of Cognitive Neuroscience: healthy younger participants (a total of 31), healthy elderly participants (a total of 36), and patients with mild cognitive impairment (a total of 43). They then gave them a task to accomplish while using virtual reality goggles that enabled genuine motions. Participants in the trial followed a route that included two straight legs connected by a turn and was marked out by numbered cones. They then had to go alone back to where they had started.

The task was carried out under three different environmental conditions designed to test the participant’s navigational abilities: a virtual setting that remained intact, one in which all ground details were temporarily replaced with a plain texture, and one in which all landmarks were temporarily removed. The study’s findings revealed that patients with early Alzheimer’s regularly underestimated the number of turns along the route and shown greater directional unpredictability. The older participants who were in good health or those who had modest cognitive impairment, however, and who did not exhibit early indicators of Alzheimer’s disease, did not exhibit these particular abnormalities.

This may aid with diagnosis since it suggests that these navigational errors are unique to Alzheimer’s disease rather than an effect of normal aging or general cognitive loss. Dr. Andrea Castegnaro, co-first author and from the UCL Institute of Cognitive Neuroscience, stated that by focusing on particular navigational errors, their findings “offer a new avenue for the early diagnosis of Alzheimer’s disease.” We are aware that additional research is necessary to support these preliminary findings.

We work to create practical tests that are simple to incorporate into clinical settings while taking into account standard limitations like time and space. It can be difficult to achieve the standards of traditional navigation exams in a therapeutic setting. Our research focuses on particular navigational features that are better suited to these limitations.We are hoping to collect enough information for a trustworthy diagnosis in a time-effective manner by developing these tests to be both quick and comprehensive, boosting the chance of their general acceptance.

In the UK, there are reportedly 944,000 dementia sufferers, and Alzheimer’s disease is assumed to be the cause of more than 60% of cases. Similar predictions suggest that, barring medical advances, the number of Americans 65 and older who have Alzheimer’s disease could double, reaching 13.8 million by 2060. These patterns show the growing toll Alzheimer’s disease is taking on healthcare systems and society at large.

For improved disease management and therapy, early diagnosis is essential. Recent developments in blood testing can now identify amounts of tau and amyloid proteins that may indicate a possible Alzheimer’s disease, however these tests might not be enough on their own. According to Dr. Castegnaro, “Cognitive exams are still required to determine when the first cognitive impairments manifest, and existing spatial memory tests used in clinics frequently depend on verbal proficiency. Our tests are designed to provide a more useful tool that is independent of language or cultural context.

REFERENCES:

https://www.healthline.com/health-news/difficulty-walking-could-be-an-early-sign-of-alzheimers-disease
https://jnnp.bmj.com/content/75/2/196
https://www.ucl.ac.uk/news/2023/oct/certain-navigational-mistakes-could-be-early-signs-alzheimers-disease

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