Glymphatic system dysfunction in Alzheimer’s disease predicts amyloid deposition, neurodegeneration, and clinical progression. The ALPS index, measuring glymphatic activity, is lower in AD patients and is linked to faster amyloid accumulation, brain atrophy, and cognitive decline.
March 2024 – Alzheimer’s & Dementia
Key takeaways
- Reduced glymphatic function is linked to accelerated amyloid accumulation, brain atrophy, and cognitive decline in Alzheimer’s disease: The glymphatic system’s dysfunction significantly correlates with increased amyloid plaque buildup in the brain, a hallmark of Alzheimer’s disease. This accumulation contributes to neurodegeneration and is associated with faster rates of brain atrophy and cognitive impairment, highlighting the importance of glymphatic function in maintaining brain health and mitigating the progression of neurodegenerative conditions
- Lower ALPS index predicts faster amyloid beta deposition and transition to amyloid-positive status: The ALPS index, an indicator of glymphatic activity, is notably lower in individuals with Alzheimer’s disease. This reduction is predictive of a more rapid increase in amyloid beta deposits, which are toxic proteins that form plaques in the brain. Individuals with a lower ALPS index are more likely to transition to an amyloid-positive status, marking the onset and progression of Alzheimer’s disease
- Glymphatic system impairment occurs before significant changes in cerebrospinal fluid biomarkers: Glymphatic dysfunction can be detected earlier than changes in traditional cerebrospinal fluid biomarkers like Aβ42. This suggests that disruptions in the glymphatic system precede and possibly contribute to the pathological processes that lead to Alzheimer’s disease, making it a potential early indicator and target for intervention
- The associations between glymphatic dysfunction and cognitive decline are mediated by amyloid deposition and brain atrophy: The relationship between reduced glymphatic function and cognitive decline is not direct but is mediated by the accumulation of amyloid plaques and subsequent brain atrophy. This means that glymphatic dysfunction leads to amyloid deposition, which in turn causes brain atrophy and cognitive deterioration, highlighting a chain of events that highlights the critical role of the glymphatic system in cognitive health
Read the article at: Huang, Shu-Yi, et al. “Glymphatic System Dysfunction Predicts Amyloid Deposition, Neurodegeneration, and Clinical Progression in Alzheimer’s Disease.” Alzheimer’s & Dementia, vol. 20, no. 5, 2024, pp. 3251-3269. Wiley Online Library, doi:10.1002/alz.13789.