Researchers at the University of South Carolina have developed a nanoparticle-based treatment that appears to improve performance on standard memory and learning tests as well as reduce brain inflammation and levels of amyloid-beta in mice with Alzheimer’s disease by converting star-shaped brain cells called astrocytes into functioning neurons.
Alzheimer’s disease remains irreversible largely because the adult brain cannot replace lost neurons; Wang et al. present a Nano-ERASER-based Trim-Away system that enables adult neuroregeneration in Alzheimer’s brain. Image credit: Wang et al., doi: 10.1016/j.celbio.2026.100575.
“Alzheimer’s disease is the most prevalent cause of dementia and remains without a therapy capable of reversing cognitive decline,” said University of South Carolina’s Professor Peisheng Xu and colleagues.
“Pathologically, Alzheimer’s disease is characterized by extracellular Aβ deposition, neurofibrillary tangles composed of hyperphosphorylated tau, synaptic loss, and neuronal death.”
“Current FDA-approved treatments, including cholinesterase inhibitors, memantine, and anti-amyloid monoclonal antibodies, offer modest symptomatic benefit or partial slowing of progression but do not halt neurodegeneration or restore lost neuronal circuits.”
“Although amyloid-lowering biologics reduce plaque burden, their clinical efficacy remains limited, and concerns such as amyloid-related imaging abnormalities, restricted patient eligibility, and high treatment burden underscore the need for alternative strategies that restore neural function through regenerative mechanisms.”
In their research, the authors studied a polymer nanogel system called Nano-ERASER that uses antibodies to degrade targeted proteins.
They used the system to permeate the blood-brain barrier and enter astrocytes, which are star-shaped support cells abundant in the central nervous system.
Within the astrocytes, Nano-ERASER deployed antibodies to break down a protein called PTBP1, triggering the astrocytes to convert to neurons.
Compared to gene-editing tools like CRISPR, Nano-ERASER does not modify DNA and its cell reprogramming is reversible.
“We hope this can be more effective and also safer,” Professor Xu said.
“We don’t need to worry about the potential side effects caused on the genetic level.”
First, the researchers applied Nano-ERASER to human astrocyte cultures, as well as human organoids designed to mimic brains with Alzheimer’s disease.
In both models, PTBP1 levels were reduced, prompting the conversion of astrocytes to neurons. Further testing revealed these new neurons were functional.
Next, the researchers treated mice with Alzheimer’s disease. Over several weeks, their nesting skills recovered, and they completed a water maze more efficiently than before, suggesting improved learning and memory.
