University of Waterloo: Mariam Malik and Her Insights

Hi everyone! I’m Mariam Malik and I am a recent graduate from the University of Waterloo, with Bachelor’s in Honours Health Sciences and Diploma in Gerontology. I am hoping to become a researcher either in health statistics or aging research. In my free time, I love reading and listening to audiobooks and I am always looking for recommendations!

Reviewed Article: Glymphatic system dysfunction predicts amyloid deposition, neurodegeneration, and clinical progression in Alzheimer's disease by Huang et al.

Main Argument & Findings:

This article focuses on the glymphatic system, a system only discovered in 2021, and how its dysfunction is associated with the development, progression and diagnosis of Alzheimer's disease (AD). The glymphatic system is a metabolic waste clearance system consisting of an intricate network of perivascular channels. Cerebrospinal fluid (CSF), the main fluid that surrounds and cushions the brain and spinal cord, carries unwanted metabolites and proteins through perivascular channels and out of the nervous system, where it is subsequently cleared via lymphatic drainage. Interestingly, this system is most active during sleep and limited during wakefulness.

Currently, AD is characterized by three main criteria: amyloid beta plaques (misfolded proteins that accumulate outside neurons), neurofibrillary tangles of tau proteins (twisted fibres of abnormal hyperphosphorylated tau protein inside neurons) and neurodegeneration. Previous research has shown that the glymphatic system eliminates these plaques and tangles. Therefore, Huang et al. hypothesized that glymphatic system dysfunction can potentially contribute to the development of AD.

Huang et al. utilized the Diffusion Tensor Image Analysis ALong the Perivascular Space (DTI-ALPS) index as a measure of glymphatic system function, where a higher ALPS index indicates more efficient waste clearance. Using this metric, the researchers found that patients with AD had a lower ALPS index compared to patients with normal cognition and mild cognitive impairment. When looking at AD biomarkers, the ALPS index is positively associated with amyloid deposition and neurodegeneration markers. This indicates that a more efficient glymphatic clearance is linked to lower amyloid accumulation and neurodegeneration. Another important finding was that a low ALPS index can predict whether a patient will have a future build-up of amyloid plaques. Therefore, this study suggests that a dysfunction of the glymphatic system contributes to the AD and glymphatic system function can serve as an early biomarker.

Usually in physiology textbooks and clinical guidelines regarding AD, it mainly discusses AD pathology as only a random build-up of proteins. However, this article helped me to understand that impaired lymphatic clearance may play an upstream role in this process.

Importance for Youth:

This information is important because it empowers youth to see brain health and the potential for cognitive decline as something they can actively protect rather than something to only worry about in older age. Understanding the role of the glymphatic system shows that lifestyle factors like adequate sleep can impact the risk of developing AD later in life. Learning about these mechanisms also highlights the importance of ongoing research and awareness, encouraging youth to stay informed about ways to support brain health.

What I Learned: 

Ultimately, I learned that AD pathology involved more than just protein accumulation, with underlying processes occurring well before symptoms appear. This suggests that early changes in brain function can occur silently, shaped by subtle factors such as sleep quality and daily routines. It has made me reconsider habits I often overlook, like keeping a consistent sleep schedule during exam season or managing stress effectively, since these small, consistent practices could have a long-term impact on cognitive health.

Citations:  Huang, S. Y., Zhang, Y. R., Guo, Y., Du, J., Ren, P., Wu, B. S., ... & Yu, J. T. (2024). Glymphatic system dysfunction predicts amyloid deposition, neurodegeneration, and clinical progression in Alzheimer's disease. Alzheimer's & Dementia, 20(5), 3251-3269. https://doi.org/10.1002/alz.13789

LinkedIn: https://www.linkedin.com/in/mariammmalik/