The organism tries to produce more to increase the probability of a protective effect
En los márgenes de un sistema sanitario desbordado, investigadores españoles han encontrado en una proteína cerebral llamada reelina una señal silenciosa del daño cognitivo que el alcohol puede infligir. Lo que comenzó como una sorpresa científica —niveles elevados de esta proteína protectora en los pacientes con peor rendimiento cognitivo— se ha convertido en una posible herramienta diagnóstica que podría cambiar el rumbo de quienes luchan contra la dependencia alcohólica. El hallazgo nos recuerda que el cuerpo, incluso cuando es dañado, intenta protegerse; y que escuchar esa señal a tiempo puede marcar la diferencia entre el deterioro y la recuperación.
- El trastorno por uso de alcohol afecta la memoria, la atención y la toma de decisiones de miles de personas, muchas de las cuales nunca reciben una evaluación neuropsicológica adecuada.
- Los pacientes con mayor deterioro cognitivo presentaban los niveles más altos de reelina en sangre, una proteína que el organismo parece producir como respuesta defensiva ante la toxicidad del alcohol.
- Una pequeña fracción de los pacientes porta la variante genética apolipoproteína E-4, que amplifica los efectos dañinos del alcohol y complica aún más su pronóstico cognitivo.
- Tras seis meses de abstinencia, tanto el deterioro cognitivo como los niveles de reelina disminuyeron, sugiriendo que el daño no es necesariamente irreversible.
- El equipo investigador continúa el seguimiento a largo plazo, con la esperanza de que este biomarcador permita derivar a los pacientes directamente a programas de rehabilitación cognitiva antes de que el deterioro se vuelva permanente.
Diagnosticar el trastorno por uso de alcohol en España suele implicar cuestionarios, análisis de sangre y, en el mejor de los casos, una evaluación psicológica. Pero en un sistema sanitario con recursos limitados, el seguimiento neuropsicológico que muchos pacientes necesitan rara vez llega. Laura Orío, investigadora de la Fundación I+12 del Hospital 12 de Octubre de Madrid, lleva tiempo buscando una solución más accesible: un simple análisis de sangre que pueda detectar el deterioro cognitivo en personas con dependencia alcohólica.
Lo que encontró su equipo fue inesperado. Los pacientes con peor rendimiento cognitivo —medido en habilidades visuoespaciales, memoria y función ejecutiva— presentaban los niveles más altos de reelina en sangre. Esta proteína existe en el cerebro como agente protector, por lo que verla elevada en los casos más graves resultó desconcertante. Además, algunos de estos pacientes portaban la variante genética apolipoproteína E-4, que agrava los efectos tóxicos del alcohol. El estudio, publicado en junio en el International Journal of Neuropsychopharmacology, incluyó 24 pacientes en abstinencia temprana y 34 personas sin el trastorno como grupo de control.
Seis meses después, en quienes habían mostrado mayor deterioro, tanto los niveles de reelina como el deterioro cognitivo habían disminuido. La psicóloga Berta Escudero, coautora del estudio, lo interpreta como un intento del organismo de compensar el daño: producir más reelina para aumentar las probabilidades de protección. Aún es pronto para establecer causalidad, pero la correlación es clara.
Más allá del laboratorio, el contexto social pesa. Francisco Pascual, presidente de Socidrogalcohol, señala que la sociedad no termina de reconocer que el alcohol provoca enfermedades más allá de la adicción misma, en parte porque está profundamente arraigado en la cultura. El alcohol se asocia a cáncer, diabetes tipo 2, enfermedades hepáticas y cardíacas, pero también al deterioro cognitivo y la demencia, con consecuencias que se extienden al trabajo y a la vida social.
El equipo continúa su investigación, rastreando a los pacientes a largo plazo y buscando biomarcadores adicionales. El objetivo final es claro: identificar a tiempo a quienes tienen deterioro cognitivo para derivarlos a programas de estimulación cognitiva, donde la mejora es posible. Como concluye el neurólogo Javier Carmiña: "Los pacientes con consumo de alcohol y disfunción cognitiva deben pedir ayuda porque es algo que puede mejorar."
Diagnosing alcohol use disorder typically means a doctor asking questions about drinking habits, running blood tests, and sometimes referring a patient for psychological evaluation. In Spain, roughly 20,000 people received this diagnosis in 2020. But many patients encounter a healthcare system stretched too thin to provide the kind of thorough neuropsychological monitoring they need. Laura Orío, a researcher at the I+12 Foundation at Madrid's Hospital 12 de Octubre, has been working on a solution: a simple blood test that could flag cognitive decline in people struggling with alcohol dependence.
Orío's team discovered something unexpected. They found that patients with the worst cognitive performance had the highest levels of a protein called reelin circulating in their blood. Reelin exists in the brain, where it helps with early development, supports normal function, and protects against damage. In the scientific community, it's generally understood as a protective molecule. "We were very surprised," Orío explains. The researchers also noticed that people with elevated reelin often carried another protein, apolipoprotein E-4, produced by a genetic mutation and present in a small fraction of the population. This variant makes alcohol's toxic effects worse in those who carry it.
The study involved 24 patients diagnosed with alcohol use disorder who were in early abstinence—four weeks without drinking—and a control group of 34 people without the disorder. Researchers assessed cognitive function using a test designed to detect cognitive impairment in alcoholism, measuring visuospatial abilities, memory, and executive function—the mental processes governing attention, concentration, and decision-making. Those who performed worst on the test also had the highest reelin levels. The findings appeared in June in the International Journal of Neuropsychopharmacology.
When patients enter treatment for alcohol dependence, they typically receive medication to manage withdrawal symptoms and group therapy. Some medications are specifically designed to reduce cravings. After six months of abstinence, the researchers checked back on their participants. In those who had struggled most cognitively, both the cognitive impairment and reelin levels had declined. It's too early to claim one causes the other, but the relationship is clear. Orío theorizes that reelin appears as the body's response to alcohol withdrawal, then gradually decreases. "The organism tries to produce more to increase the probability of a protective effect," says Berta Escudero, the study's other lead author and a psychologist at the same foundation.
Reelin levels vary based on other factors too—how long someone has been drinking and how much. Prolonged alcohol use causes inflammation and changes in the brain that can accumulate into structural damage, according to Javier Carmiña, a spokesperson for the Spanish Society of Neurology. Alcohol use disorder connects to cancer, type 2 diabetes, liver and heart disease, but it also damages mental health and can cause cognitive decline and dementia. Beyond the medical consequences, it disrupts work and social life. Yet the condition remains underdiagnosed. Francisco Pascual, president of Socidrogalcohol, a nonprofit scientific society focused on addiction treatment and prevention, points out that society doesn't fully grasp that alcohol causes diseases beyond addiction itself. "It's part of our tradition, our deepest identity, that we celebrate everything with alcoholic drinks."
Cognitive rehabilitation training specifically targets executive function and short-term memory—abilities most people need for daily life. Once someone stops drinking, cognitive improvements often follow, particularly in attention, though the degree of recovery depends heavily on how much alcohol they consumed during their addiction. The research team is continuing their work, tracking patients long-term to understand the mechanism linking reelin to cognitive decline in alcohol use disorder, and searching for additional biomarkers. All four experts agree this finding could make a real difference. Identifying people with cognitive impairment would allow them to be referred directly to cognitive stimulation programs, where they might stabilize or even improve rather than decline. "Patients with alcohol use and cognitive dysfunction should seek help because it's something that can improve," Carmiña concludes.
Citas Notables
We were very surprised. In the scientific community reelin is understood as a good protein.— Laura Orío, researcher at Hospital 12 de Octubre
Patients with alcohol use and cognitive dysfunction should seek help because it's something that can improve.— Javier Carmiña, Spanish Society of Neurology
La Conversación del Hearth Otra perspectiva de la historia
Why does reelin show up in the blood when someone's brain is damaged by alcohol? It seems backwards—shouldn't a protective protein be lower when things are worse?
That's exactly what surprised the researchers. Reelin is protective, but it appears to spike as a kind of emergency response when the brain is injured. Think of it as the body trying harder to repair damage. Once someone stops drinking and the brain begins healing, reelin levels drop back down.
So the protein itself isn't the problem—it's a signal that the problem exists?
Precisely. It's like a smoke detector going off. The smoke detector isn't causing the fire; it's telling you the fire is there. In this case, high reelin means cognitive damage is present.
Why does this matter for treatment? Can't doctors already tell when someone's cognition is declining?
They can, but it takes time and specialized testing that many healthcare systems can't provide. A blood test is fast, cheap, and objective. It could flag people who need cognitive rehabilitation before they get worse.
And the genetic factor—the APOE-4 mutation—does that change how doctors should treat someone?
It suggests that some people are more vulnerable to alcohol's damage. If you carry that variant, your brain suffers more harm from the same amount of drinking. It's not yet clear how that should change treatment, but it's important information.
What happens to these patients after they get identified and start cognitive rehab?
The research shows improvement is possible. After six months sober, cognitive function and reelin levels both improved. But recovery depends on how long and how much someone drank. The damage isn't always reversible, but stopping drinking gives the brain a real chance.