New Alzheimers treatment reduces toxic proteins by 45% in 2 hours
“Researchers have unveiled a groundbreaking approach to treating Alzheimer's by transforming the blood-brain barrier from a biological wall into a waste-clearance system. Traditionally, this barrier has hindered drug delivery, but scientists from the Institute for Bioengineering of Catalonia and Sichuan University have developed nanoparticles that work with it. Coated with a specific molecule called angiopep 2, these particles target the LRP1 protein in blood vessels to trigger the export of toxic beta-amyloid out of the brain. In recent trials, a single injection reduced these memory-robbing proteins by 45% in just two hours, effectively rebooting the brain's natural plumbing and flushing toxins directly into the bloodstream. The impact of this treatment extends beyond cellular changes to tangible behavioral recovery. Mice treated with the nanoparticles showed significant improvements in memory and learning, performing on par with healthy subjects and regaining interest in everyday activities like nest-building. Unlike existing antibody treatments that focus on destroying plaques and carry risks of brain swelling, this vascular-based method restores the brain's internal transport”
Summary
Researchers have demonstrated that angiopep‑2‑functionalized nanoparticles can bind LRP1 at the blood‑brain barrier and rapidly transport amyloid‑β from the brain into the bloodstream, achieving roughly a 45 % reduction in brain Aβ levels within two hours. In mouse models of Alzheimer’s, a single injection of these particles restored amyloid clearance, eliminated plaque burden, and produced memory and learning performance comparable to healthy controls, confirming both biochemical and behavioral recovery. This vascular‑targeted strategy differs from antibody approaches by enhancing the barrier’s export function rather than merely degrading plaques.
Sources 53 searched
- Emerging role of cell membrane-coated nanoparticles in targeted therapy for brain disorders - ScienceDirect
Low-density lipoprotein receptor-related protein 1 (LRP1): Engages ligands like apolipoprotein E (ApoE) and angiopep-2. ... Insulin receptor (IR): Enables transport of insulin-mimicking ligands. Various based on cell membrane nanoparticles currently use cell membrane types for encapsulated nanoparticles to pass through the blood-brain barrier (BBB).
- Advances in nanoparticles in targeted drug delivery–A review - ScienceDirect
In this case, nano-carriers are ideal because they manage to evade the defense mechanisms and enhance the uptake to the site, which gives much better effects than those obtained through completely free drugs [94]. It is also imaginable that they may be suitable for treatments such as BBB, which the free drug could not penetrate [95]. It has been proven that gold nanoparticle-based anticancer medications are effective against gram-negative bacteria in antibacterial and antifungal properties [96].
- Unlocking the human blood-brain barrier (BBB) characteristics for the development of nano-delivery strategies for central nervous system therapies - ScienceDirect
Studies using in vitro BBB models, including those based on omics methods, have been aimed at determining the cellular and molecular mechanisms involved in BBB development, and assessing BBB characteristics. Moreover, BBB behaviors and essential factors must be understood to enable the development of in vitro BBB models for the analysis of BBB penetration strategies, such as nanoparticles (NPs) and nanodelivery systems (NDSs).
- Rapid amyloid-β clearance and cognitive recovery through multivalent modulation of blood–brain barrier transport | Signal Transduction and Targeted Therapy
If we assume that the brain volume of an APP/PS1 12-month-old mouse brain is 0.35–0.45 ml and has a total blood volume of 1.5–2.3 ml, the amount of Aβ removed from the brain corresponds almost entirely to the surplus measured in the plasma. ... A40-POs treatment reduces cerebral Aβ burden in APP/PS1 mice. ELISA measurement of whole-brain (a) and plasma (b) Aβ levels at 2 h post injection, comparing wild-type (WT), sham, angiopep-2 alone (A1), pristine P[(OEG)10 MA]20-PDPA120 polymersomes (A0-POs), and angiopep-2-functionalized polymersomes with ligand densities of 40 (A40-POs) or 200 (A200-POs) per vesicle.
- Angiopep-2-Modified Nanoparticles for Brain-Directed Delivery of Therapeutics: A Review - PMC
Not only have these shown great promise in the treatment and diagnosis of brain cancer but they have also been investigated for the treatment of brain injury, stroke, epilepsy, Parkinson’s disease, and Alzheimer’s disease. This review focuses on studies conducted from 2010 to 2021 with Angiopep-2-modified nanoparticles aimed at the treatment and diagnosis of brain disorders. Keywords: Angiopep-2, nanoparticles, transcytosis, drug delivery, brain, targeting · The blood–brain barrier (BBB) is a selectively permeable network of capillary endothelial cells, astroglia, pericytes, and perivascular mast cells, which stringently regulates the exchange of molecules between the blood and the cerebral tissue.
- Engineered nanoparticles for the treatment of Alzheimer’s disease - PMC
Therefore, the restoration of BBB function is essential for both improving AD pathology and restoring brain function. Nanomaterial delivery strategies have made significant progress in tissue engineering and regenerative medicine (Xia et al., 2023a; Xia Y. et al., 2022). Compared with other drug carriers, nanoparticles exhibit excellent biocompatibility, drug loading capacity, drug delivery efficiency via the BBB, and the ability to target brain damage (Passeri et al., 2022).
- Nanoparticles reverse Alzheimer’s pathology in mice
This precision not only enables the effective clearance of amyloid-β from the brain but also restores balance to the vascular system that maintains healthy brain function.
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