Scientists from the Federal University of Rio de Janeiro (UFRJ), in collaboration with the University of São Paulo (USP), have discovered that a molecule called hevina can reverse cognitive deficits in mice. The study revealed that this glycoprotein, produced by brain cells known as astrocytes, boosts the formation of synapses—connections between neurons—in aged rodents and in experimental models of Alzheimer’s disease.
“Hevina is a well-known molecule involved in neural plasticity,[…]It is naturally secreted by astrocytes, cells that support neuronal function. Our research shows that hevina overproduction can reverse age-related cognitive decline by improving synaptic quality.”
– Dr. Flávia Alcantara Gomes, head of the Cellular Neurobiology Laboratory at UFRJ’s Institute of Biomedical Sciences.
The research, published in the journal Aging Cell, was supported by Brazil’s Ministry of Health, the Carlos Chagas Filho Foundation (Faperj), and the São Paulo Research Foundation (FAPESP).
A Long Road Ahead
Despite the promising results, researchers caution that the findings are from basic science and tested only in mice. Developing a drug based on hevina would require overcoming significant challenges, including ensuring the molecule can cross the blood-brain barrier, which protects the brain from harmful substances.
“Eventually, we may design drugs that mimic hevina’s effects,” Gomes noted. “But the main achievement for now is a deeper understanding of the cellular and molecular mechanisms of Alzheimer’s and aging. The novelty lies in recognizing astrocytes—not just neurons—as potential therapeutic targets.”
Evidence-Based Hypothesis
Analyzing public data, researchers found that hevina levels are lower in the brains of Alzheimer’s patients compared to healthy individuals of the same age. Using this information, the UFRJ team introduced a viral vector to stimulate hevina production in the astrocytes of aged mice and genetically modified mice mimicking Alzheimer’s symptoms.
They also analyzed the brain proteome —the full set of proteins expressed in the brain. The team found that 89 proteins were differently expressed in mice with elevated hevina levels. This proteomic analysis was carried out at the Redox Proteomics Core Laboratory at USP’s Institute of Chemistry, part of FAPESP’s Redoxoma research center.
“Synapses rely on specific proteins to transmit chemical signals between neurons,” explained Dr. Danilo Bilches Medinas of USP. “Our data show that hevina enhances the production of proteins linked to synapse formation. As a result, we saw improved cognitive performance and increased neuronal connectivity.”
Amyloid Plaques Remain
Interestingly, although the cognitive abilities of Alzheimer’s-model mice improved, the amount of beta-amyloid plaques —a hallmark of the disease—remained unchanged in the hippocampus. This finding challenges the long-standing focus on these plaques in Alzheimer’s drug development.
“To our surprise, cognitive recovery occurred without changes in plaque levels,” said Felipe Cabral-Miranda, a biomedical scientist at UFRJ and lead author of the study. “This supports the idea that Alzheimer’s has multiple causes. Some elderly people show plaques in their brains but no cognitive symptoms.”
Cabral-Miranda added, “While the role of amyloid plaques is still debated, our results support the hypothesis that they are not the root cause of Alzheimer’s. A molecule like hevina can improve cognition even without affecting plaque levels.”
The discovery opens new doors for understanding and potentially treating cognitive decline. It also emphasizes the importance of astrocytes, often overshadowed by neurons, in brain health and disease.