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The Impact of Blood-Brain Barriers on Alzheimer's Disease

By: Sai Srihaas Potu

Alzheimer's disease (AD) is a major public health problem that affects approximately 4.5 million Americans with prevalence estimates exceeding 14 million within a generation. Current research has focused on developing reliable biomarkers and cognitive tests that discriminate between normal aging, mild cognitive impairment, and AD. These strategies may enable clinicians to make an early diagnosis and identify at-risk individuals who would receive the greatest benefit from newly developed therapies. If these therapeutic strategies are to succeed, a dementia screening program to identify at-risk individuals at the earliest possible stage will need to be developed.


However, there are currently no clear guidelines for dementia screening of the general population or knowledge of how receptive older adults would be to discussing memory problems with their health care providers.


In a new study, researchers discovered that a focused ultrasound targeting the hippocampus may induce an immunological healing response for those with Alzheimer’s disease. West Virginia University scientists used MRI scans to show what happens when ultrasound waves target a specific area of Alzheimer’s patient’s brains. They concluded that this treatment may induce an immunological healing response, a potential breakthrough for a disease that accounts for up to 80% of all dementia cases.


Rashi Mehta, a researcher with the WVU School of Medicine and Rockefeller Neuroscience Institute, led the study. In 2018, WVU launched a first-of-its-kind clinical trial to explore the use of focused ultrasound to open the blood-brain barrier in early-stage Alzheimer’s patients.


The blood-brain barrier has long presented a challenge in treating the most pressing neurological disorders. The ability to noninvasively and reversibly open the blood-brain barrier in deep brain areas, such as the hippocampus, offers new potential in developing treatments for Alzheimer’s disease.


The ultrasound targeted the hippocampus in particular because it plays a large role in learning and memory. Dr.Mehta used MRI with contrast-enhancement dye to observe the changes that took place in the brains of three early-stage Alzheimer’s patients–ages 61, 72, and 73–who underwent the ultrasound treatment. She observed that the dye moved along the course of draining veins following the procedure.


According to the researchers, this imaging pattern was unexpected and enhances our understanding of brain physiology. The glymphatic system, which is a fluid-movement and waste-clearance system that’s unique to the brain, has been studied in animals, but there is controversy about whether this system truly exists in humans. The imaging pattern that the researchers discussed in the paper offers evidence not only to support that the system does likely exist in humans but that focused ultrasound may modulate fluid movement patterns and immunological responses along this system.


Dr.Mehta and her colleagues’ analysis of the MRI scans suggests that an immunological healing response may occur around the draining veins following the procedure. It is important to ask why amyloid levels are so important. Unusually high amounts of this protein tend to clump together in the brains of Alzheimer’s patients, forming plaques between nerve cells and sabotaging their function. The ongoing clinical trial aims to assess whether focused ultrasound can reduce amyloid plaques in patients with Alzheimer’s disease.


This project did not involve any medications. The ultrasound itself was enough to elicit a probable immunological response. In the future, however, the treatment may make it easier to medicate the brain with more precision, even in people who don’t have Alzheimer’s disease.


As Dr.Mehta and her team enroll more participants, they plan to examine the treatment’s long-term effects. They want to know whether it is safe and effective for slowing–or even reversing–the progression of Alzheimer’s dementia.


Alzheimer’s disease is the nation’s most common form of dementia, and it’s on the rise. The Alzheimer’s Association reports that 5.8 million Americans age 65 and older had Alzheimer’s dementia in 2020. By 2050, that number could rise to 13.8 million. The focused ultrasound team at RNI is committed to improving the lives of patients with Alzheimer’s disease by pioneering advances using a truly integrated approach and the latest technologies.


Like all types of dementia, Alzheimer’s develops due to the death of brain cells. It is a neurodegenerative condition, which means that brain cell death happens over time. In a person with Alzheimer’s, the brain tissue has fewer and fewer nerve cells and connections, and tiny deposits, known as plaques and tangles, build upon the nerve tissue.


Plaques develop between the dying brain cells. They are made from a protein known as beta-amyloid. The tangles, meanwhile, occur within the nerve cells. They are made from another protein, called tau.


Researchers do not fully understand why these changes occur. Several factors may be involved. The Alzheimer’s Association has produced a visual guide to show what happens in the process of developing Alzheimer’s disease.


Alzheimer’s disease is a neurodegenerative condition. A buildup of plaques and tangles in the brain, along with cell death, causes memory loss and cognitive decline. There is currently no cure, but drugs and other treatments can help slow or ease the cognitive, emotional, and behavioral symptoms and improve the person’s quality of life. Researchers should continue to work to develop new treatment options so that affected patients can live better lives.



References:

1. Csernansky JG, Wang L, Swank J, et al. Preclinical detection of Alzheimer's disease: hippocampal shape and volume predict dementia onset in the elderly. NeuroImage. 2005.

2. Rashi Mehta et al. Blood-Brain Barrier Opening with MRI-guided Focused Ultrasound Elicits Meningeal Venous Permeability in Humans with Early Alzheimer Disease. Radiology. 2021.

3. Werner P. Knowledge about symptoms of Alzheimer’s disease: correlates and relationship to help-seeking behavior. International Journal of Geriatric Psychiatry. 2003.

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