For decades, the dominant theory of Alzheimer’s disease has revolved around amyloid plaques—sticky protein deposits that accumulate in the brain and are thought to drive neurodegeneration. However, new research from Lund University, published in Nature Aging, challenges this long-standing belief. The study suggests that the real culprits behind Alzheimer’s may not be the plaques themselves but rather protofibrils—smaller, more soluble aggregates of amyloid-beta (Aβ) that accumulate when the brain's fluid drainage system breaks down.
This shift in understanding has significant implications for both diagnosing and treating Alzheimer’s. Rather than solely targeting plaque removal, researchers and clinicians may need to prioritize restoring the brain's natural clearance mechanisms, a strategy that aligns closely with Ciatrix's focus on cerebrospinal fluid (CSF) dynamics.
The Aβ42 to Aβ40 Ratio and Protofibrils
The Aβ42 to Aβ40 Ratio: a biomarker for Alzheimer's disease
Aβ42 and Aβ40 are two types of amyloid-beta proteins found in cerebrospinal fluid. Aβ42 is more likely to form clumps, while Aβ40 remains more soluble. The ratio of Aβ42 to Aβ40 is often used as a biomarker for Alzheimer’s disease because a decreasing ratio may indicate that Aβ42 is being trapped in the brain rather than flowing freely in the CSF.
What Did the Study Find?
The Lund University research team found that the ratio of Aβ42 to Aβ40 in CSF was more strongly correlated with protofibril accumulation than with plaques. In other words, as Alzheimer’s progresses, declining CSF Aβ levels may indicate an increase in toxic protofibrils rather than a direct reflection of plaque formation.
These protofibrils appear to be the real disruptors in Alzheimer's disease, correlating with markers of brain cell damage, such as total tau and neurofilament light (NfL), which are linked to cognitive decline. This suggests that plaques might be more of a side effect rather than the root cause of the disease. If protofibrils are the real drivers, we need to rethink how we diagnose and treat Alzheimer’s—focusing more on clearing these toxic protein clumps rather than just targeting plaque removal.
The Brain’s Plumbing System: Why Drainage Matters More Than Deposits
The Glymphatic System and Alzheimer’s Risk
The human brain has a sophisticated fluid clearance system that functions much like a plumbing network, flushing out toxins and metabolic products. This system, known as the glymphatic system, relies on cerebrospinal fluid to wash away waste, including excess amyloid-beta.
But when this clearance system fails, toxic proteins like protofibrils can accumulate, leading to neuroinflammation and cell damage. Disruptions in the glymphatic system play a critical role in the development of Alzheimer's disease. Instead of solely focusing on amyloid plaques, it is crucial to restore and optimize CSF circulation to keep the brain healthy.
How Spinal Movements and Deep Relaxation Could Enhance Brain Drainage
The Connection Between Movement, Relaxation, and CSF Circulation
Spinal movement and deep relaxation techniques may naturally enhance CSF circulation.
Non-REM sleep and deep relaxation states, such as those achieved through meditation, have been linked to enhanced glymphatic activity, facilitating the removal of toxic protein aggregates.
Rhythmic spinal motion, observed during stretching, walking, or even specific breathing exercises, can improve CSF circulation, potentially supporting better waste clearance in the brain.
Integrating deep relaxation with rhythmic spinal movement, such as in yoga or qigong, may further promote the clearance of protofibrils and other neurotoxic substances, optimizing brain health.
By combining these practices—spinal movement, targeted physical therapies, and sleep-optimized interventions—we could enhance CSF circulation, supporting the brain’s natural waste-clearing mechanisms.
What This Means for the Future of Alzheimer’s Treatment
A Shift from Amyloid-Centric Therapies to Fluid Restoration
Traditional Alzheimer's treatments have largely focused on removing plaques, yet clinical trials targeting amyloid have fallen short in slowing cognitive decline. The findings from Lund University suggest a new path forward:
Developing biomarkers that track protofibril accumulation rather than just plaque burden.
Therapies aimed at enhancing glymphatic clearance, including sleep optimization, spinal motion exercises, and CSF modulation.
Non-invasive monitoring of brain fluid flow through advanced imaging techniques like DTI-ALPS (Diffusion Tensor Imaging with Analysis along the Perivascular Space) and wearable fNIRS technology (Functional Near-Infrared Spectroscopy).
By focusing on fluid flow and natural clearance mechanisms, we may finally be able to intervene earlier and more effectively in Alzheimer’s progression.
A New Era in Brain Health
The discovery that protofibrils, not plaques, may be the driving force behind Alzheimer’s represents a major paradigm shift in our understanding of neurodegeneration. It reinforces the idea that Alzheimer’s may be more of a drainage problem than a deposition problem, highlighting the importance of maintaining optimal cerebrospinal fluid circulation.
At Ciatrix, we are exploring new strategies that focus on restoring the brain's natural waste-clearance mechanisms, incorporating spinal movement-based techniques to enhance cerebrospinal fluid circulation. The future of Alzheimer’s lies not in simply removing plaques but in utilizing the body’s ability to clear toxins and restore homeostasis.
Could improving glymphatic function be the most promising approach to Alzheimer’s? The evidence is growing.
References
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