Rapid amyloid-β clearance and cognitive recovery through multivalent modulation of blood–brain barrier transport, 2025, Xiang et al.

[Chandelier]

Rapid amyloid-β clearance and cognitive recovery through multivalent modulation of blood–brain barrier transport - Signal Transduction and Targeted Therapy

The blood‒brain barrier (BBB) is a highly selective permeability barrier that safeguards the central nervous system (CNS) from potentially harmful substances while regulating the transport of essential molecules. Its dysfunction is increasingly recognized as a pivotal factor in the pathogenesis...

www.nature.com

Spoiler: Authors

• Junyang Chen,
• Pan Xiang,
• Aroa Duro-Castano,
• Huawei Cai,
• Bin Guo,
• Xiqin Liu,
• Yifan Yu,
• Su Lui,
• Kui Luo,
• Bowen Ke,
• Lorena Ruiz-Pérez,
• Qiyong Gong,
• Xiaohe Tian &
• Giuseppe Battaglia

Abstract​

The blood‒brain barrier (BBB) is a highly selective permeability barrier that safeguards the central nervous system (CNS) from potentially harmful substances while regulating the transport of essential molecules.
Its dysfunction is increasingly recognized as a pivotal factor in the pathogenesis of Alzheimer’s disease (AD), contributing to the accumulation of amyloid-β (Aβ) plaques.

We present a novel therapeutic strategy that targets low-density lipoprotein receptor-related protein 1 (LRP1) on the BBB.
Our design leverages the multivalent nature and precise size of LRP1-targeted polymersomes to modulate receptor-mediated transport, biasing LRP1 trafficking toward transcytosis and thereby upregulating its expression to promote efficient Aβ removal. In AD model mice, this intervention significantly reduced brain Aβ levels by nearly 45% and increased plasma Aβ levels by 8-fold within 2 h, as measured by ELISA. Multiple imaging techniques confirmed the reduction in brain Aβ signals after treatment.

Cognitive assessments revealed that treated AD mice exhibited significant improvements in spatial learning and memory, with performance levels comparable to those of wild-type mice.
These cognitive benefits persisted for up to 6 months post-treatment.

This work pioneers a new paradigm in drug design, where function arises from the supramolecular nature of the nanomedicine, harnessing multivalency to elicit biological action at the membrane trafficking level.
Our findings also reaffirm the critical role of the BBB in AD pathogenesis and demonstrate that targeting the BBB can make therapeutic interventions significantly more effective.

We establish a compelling case for BBB modulation and LRP1-mediated Aβ clearance as a transformative foundation for future AD therapies.

 

[rvallee]

In AD model mice, this intervention significantly reduced brain Aβ levels by nearly 45% and increased plasma Aβ levels by 8-fold within 2 h, as measured by ELISA. Multiple imaging techniques confirmed the reduction in brain Aβ signals after treatment.

The contrast between the incredible breakthroughs of biomedicine, thousands and thousands, continues to be comically out of proportion with the mediocrity produced under a biopsychosocial evidence-based medicine paradigm, which doesn't have a single one to date, not even a minor one. Can't even talk about orders of magnitude of difference because dividing by zero is invalid.

It's literally the difference between magic and science. Science works. Magic is a bunch of fairy tales for children (and also plenty of weird mythology).

 

[Chandelier]

New Alzheimer's Treatment Clears Plaques From Brains of Mice Within Hours

Scientists have repaired a natural gateway into the brains of mice, allowing the clumps and tangles associated with Alzheimer's disease to be swept away.

www.sciencealert.com

AI Summary;

A groundbreaking Alzheimer's treatment has shown remarkable results in mice, clearing nearly 45% of amyloid-beta plaques from their brains within hours of a single injection. These plaques are a major hallmark of Alzheimer's disease. After three doses, mice that previously showed cognitive decline performed just as well as healthy mice in memory and learning tests. The improvements lasted for at least six months.

The treatment, developed by researchers from Spain and China, targets the blood-brain barrier (BBB), a protective gateway that often becomes dysfunctional in Alzheimer’s. Instead of forcing drugs across this barrier, the new approach repairs it, allowing the brain to clear out harmful protein clumps naturally.

The researchers used specially designed nanoparticles not simply to deliver drugs, but to actively restore the brain’s clearance systems. These nanoparticles targeted endothelial LRP1, a protein that helps remove waste like amyloid-beta. Once the BBB’s transport mechanisms were repaired, the brain regained its ability to remove these toxic proteins on its own.

This method offers a promising alternative to current treatments, which have had limited success and cannot reverse the disease. While drugs like lecanemab slow Alzheimer’s progression, they do not restore brain function.

Although the study was conducted on a specific mouse model, and results may not directly translate to humans, experts believe it supports a growing view: Alzheimer’s might begin at the brain’s borders, not just within it. Repairing the BBB could therefore represent a new and powerful direction in treating neurodegenerative disease.