New Surgery for Alzheimer’s Targets The Brain’s Waste Removal System

Unclogging the Brain’s Pathways: A New Hope in Alzheimer’s Research

Developing treatments for Alzheimer’s disease (AD) and other dementias has long been one of the most daunting challenges in neuroscience and medicine. Despite decades of effort and significant advancements in understanding the disease, a definitive cure remains out of reach. Many therapies have focused on targeting amyloid-beta (Aβ) plaques or tau tangles, but even after more than 2,700 clinical trials, attempts to develop disease-modifying therapy for Alzheimer's have largely failed. These setbacks have driven researchers to explore new and unconventional approaches, shifting attention toward the brain’s own waste-clearing mechanisms.

Understanding the Glymphatic System’s Role in Brain Health

Discovered just over a decade ago, the glymphatic system is the brain’s natural mechanism for clearing out waste. It relies on cerebrospinal fluid (CSF) to flush out various byproducts, including Aβ and tau, proteins associated with Alzheimer’s disease. When this system becomes impaired—as it often does with age—protein deposits may accumulate, potentially contributing to neuroinflammation and cognitive decline. While the exact role of Aβ and tau in Alzheimer’s is still debated, emerging research suggests that improving glymphatic function could help slow, halt, or even reverse some aspects of AD.

This waste clearance system relies on the meningeal lymphatic vessels and deep cervical lymph nodes, which ultimately play an important role in draining CSF and metabolic byproducts. Research has shown that these systems are interconnected, and impairments in one can exacerbate dysfunction in the other, further increasing the risk of cognitive decline. This understanding has prompted new studies exploring how both systems can be optimized for better brain health.

The Challenges of Glymphatic Dysfunction

As researchers study the glymphatic system more closely, they are learning more about why its efficiency declines with age. One major factor is the structural rigidity of the brain’s perivascular spaces, which hinders the flow of cerebrospinal fluid. Additionally, chronic inflammation—commonly associated with aging—can impair the function of astrocytes, the glial cells that regulate glymphatic activity. Sleep quality, hydration, and even posture and spinal motions also appear to influence glymphatic flow, offering insight into potential lifestyle interventions that might complement medical approaches.

Aging also affects the deep cervical lymph nodes, which serve as critical drainage points for the glymphatic system. Declining lymphatic node function can lead to increased CSF pressure and impaired clearance of neurotoxic substances, further accelerating the progression of conditions like Alzheimer’s. Understanding how these peripheral structures contribute to brain health is key to developing effective interventions.

A Novel Surgical Approach

A research team in Shanghai recently tested a procedure called Cervical Shunting to Unclog Lymphatic Systems (CSULS), demonstrating the role of innovation in advancing Alzheimer's research. This minimally invasive surgery connects deep cervical lymphatic vessels to veins, reducing blockages in the glymphatic system and helping to clear out waste from the brain. The procedure is safer than traditional intracranial surgeries and has already shown promise in early trials.

Six patients with Alzheimer’s have undergone the surgery so far. Post-operative assessments revealed improvements in cognitive performance, including attention and reaction time.

Caregivers also noted better language skills, mood, and improvements in memory function. In one case, a 70-year-old woman showed significant improvements in symptoms, such as memory loss, along with reduced levels of tau proteins in her brain just five weeks after the surgery. Her daughter shared, “My mother’s memory is stabilizing and improving.”

Moreover, brain imaging, including PET scans, revealed increased glucose metabolism in areas affected by Alzheimer’s, suggesting enhanced brain activity. These scans also showed reduced tau accumulation, particularly in the temporal lobes. Such measurable changes provide objective evidence of the potential benefits of CSULS.

Although this is still early-stage research, the results are encouraging and suggest that improving glymphatic flow could offer a new way to treat Alzheimer’s.

Why CSULS is a Unique New Surgery for Alzheimer’s

What sets the CSULS procedure apart from other approaches is its focus on extracranial intervention. By avoiding the need to operate directly on the brain, the surgery reduces risks associated with brain operations while still addressing the underlying glymphatic dysfunction.

The use of supermicrosurgical techniques to create lymphatic-venous connections demonstrates how advancements in surgical technology can open doors to previously unattainable treatments.

This approach allows for precise manipulation of the lymphatic system, reducing high-pressure bottlenecks and enhancing fluid drainage without the need for invasive brain surgery.

Additionally, the procedure highlights the growing trend of addressing peripheral systems, like the cervical lymphatic network, to improve central nervous system health. This shift in focus opens up new possibilities for treating neurodegenerative diseases more broadly.

A Broader Perspective: Observational Research

In a parallel effort, researchers at Zhejiang University are studying a similar approach called Deep Cervical Lymphatic-Venous Anastomosis (DCLVA). This procedure also focuses on enhancing CSF drainage through the cervical lymph nodes. The lymphatic system often loses efficiency with age and chronic inflammation, leading to increased pressure in the brain and worsening protein accumulation. By restoring drainage, researchers hope to alleviate these issues and slow the disease’s progression.

Potential Impact of DCLVA

The DCLVA study highlights the importance of targeting systemic factors in Alzheimer’s treatment. The cervical lymph nodes, serving as the final drainage point for glymphatic waste, highlight the important connection between peripheral systems and brain health. Additionally, this research raises questions about whether improving lymphatic flow might have broader applications for other neurodegenerative diseases, such as Parkinson’s or multiple sclerosis.

Preclinical animal studies have already shown that enhancing meningeal lymphatic function can improve cognitive performance and reduce protein accumulation in the brain. These findings align with the potential benefits observed in early human trials, suggesting a broader application for techniques like DCLVA.

Although this study is still in its early stages, it reflects the growing focus on glymphatic dysfunction as a key target for Alzheimer’s treatment.

The Role of Imaging in Tracking Progress

Advanced imaging techniques have played a crucial role in evaluating the success of both CSULS and DCLVA. PET scans, particularly those using tau tracers, have been instrumental in measuring changes in protein accumulation. Additionally, diffusion tensor imaging (DTI) has provided insights into fluid dynamics along the brain’s perivascular spaces, helping researchers assess improvements in glymphatic flow.

These imaging tools not only validate the efficacy of surgical interventions but also offer a means to monitor disease progression and treatment outcomes over time. This ability to track changes quantitatively is vital for refining these procedures and integrating them into broader treatment protocols.

Hope for the Future of Alzheimer’s Treatment

Although the field of Alzheimer’s research has faced many setbacks, studies like CSULS and DCLVA represent a promising shift toward innovative approaches. These techniques demonstrate how addressing the brain’s natural waste-clearance mechanisms can complement existing therapies and open new doors for managing the disease.

By focusing on the glymphatic and lymphatic systems, researchers are not only targeting Alzheimer’s at its roots but also paving the way for broader applications in neurodegenerative and other brain diseases. While much work remains to be done—including larger clinical trials and long-term follow-ups—these early successes remind us that progress is possible.

For patients and their families, these advancements provide a glimmer of hope. With every discovery, we move closer to understanding and managing Alzheimer’s in ways that once seemed out of reach.

References:

1. Mogensen FL-H, Delle C, Nedergaard M. The Glymphatic System (En)during Inflammation. International Journal of Molecular Sciences. 2021; 22(14):7491. https://doi.org/10.3390/ijms22147491

2. Xiong Y, Yu Q, Zhi H, et al. Advances in the study of the glymphatic system and aging. CNS Neurosci Ther. 2024; 30:e14803. doi:10.1111/cns.14803

3. Reddy OC, van der Werf YD. The Sleeping Brain: Harnessing the Power of the Glymphatic System through Lifestyle Choices. Brain Sciences. 2020; 10(11):868. https://doi.org/10.3390/brainsci10110868

4. Li, X., Zhang, C., Fang, Y., et al. (2024). Promising outcomes 5 weeks after a surgical cervical shunting procedure to unclog cerebral lymphatic systems in a patient with Alzheimer’s disease. Shanghai Jiao Tong University.

5. Zhejiang University. (2024). A Pilot Study of Deep Cervical Lymphatic-Venous Anastomosis in the Treatment of Alzheimer’s Disease. ClinicalTrials.gov Identifier: NCT06448442.