Researchers at the University of Wisconsin–Madison have developed a method to grow neurons from human stem cells using a protein called ACTIVIN-A. This breakthrough creates a living model to study how Alzheimer’s disease progresses, with findings published in Nature.
Alzheimer’s disease stands as the most common form of dementia. It is a neurodegenerative condition marked by the gradual loss of neuron function. The focus of the new study is on the LC-NE neurons of the locus coeruleus, a compact cluster of nerve cells deep within the brainstem.
These neurons influence heart rate and blood pressure while playing a key role in memory and attention. Notably, they begin to deteriorate early in Alzheimer’s, sometimes years before widespread brain dysfunction becomes evident.
The research team aimed to craft a model that faithfully mirrors the behavior of locus coeruleus neurons. Earlier efforts to generate these cells from human stem cells—using mouse systems—did not yield successful results. The scientists discovered that ACTIVIN-A actively participates in neurogenesis, the process of forming new, functioning neurons, enabling the creation of viable LC-NE neurons in vitro.
In the experimental process, human stem cells were guided toward hindbrain lineage to become artificial LC-NE neurons. ACTIVIN-A was then applied to enhance neuronal maturation and viability. The resulting cells extended axons and developed dendritic branches, demonstrating the capacity to transmit electrical signals from the cell body to target tissues and neighboring neurons.
According to the researchers, this breakthrough offers a versatile platform to investigate the development of neurodegenerative diseases such as Alzheimer’s disease. Beyond modeling disease progression, the artificially grown neurons provide a testbed for evaluating drug candidates and therapeutic approaches in a controlled human cell context.
The study’s implications extend to a deeper understanding of how early brain changes unfold and how targeted interventions might alter the disease trajectory. With a human-cell-based system, scientists can probe the specific biology of locus coeruleus neurons and their role in cognitive function, attention, and autonomic regulation—areas that are often affected in the preclinical stages of Alzheimer’s disease.
In addition to advancing disease modeling, this approach offers a practical route to screen potential treatments for efficacy and safety before moving into animal or clinical testing. The ability to reproduce key features of LC-NE neurons in a laboratory setting supports a more precise exploration of how these cells contribute to brain health and how their dysfunction may drive aging-related cognitive decline.
Ultimately, the development of an ACTIVIN-A–driven model of locus coeruleus neurons represents a meaningful step toward bridging basic biology and therapeutic discovery. By providing a faithful, human-derived platform, researchers can accelerate insights into the pathophysiology of Alzheimer’s disease and related dementias while refining strategies to protect memory, attention, and overall neural resilience.