Long COVID May Trigger Alzheimer's-Like Brain Changes, New Study Warns

A groundbreaking study from NYU Langone Health reveals a troubling connection between long COVID and the brain changes associated with Alzheimer's disease. Researchers discovered that people with long COVID show structural changes in a critical brain region that mirrors patterns seen in early Alzheimer's disease, raising concerns about potential long-term cognitive decline in millions of people worldwide who continue to experience lingering symptoms months or years after their initial COVID-19 infection.

What Is the Choroid Plexus and Why Does It Matter?

The choroid plexus is a network of blood vessels lined with specialized cells that produce cerebrospinal fluid, the fluid that cushions your brain and protects it from injury. Think of it as your brain's waste management and immune system rolled into one. This tiny but mighty structure regulates inflammation in the brain and clears out harmful waste products. Past research has shown that the COVID-19 virus can directly damage the cells lining these blood vessels, potentially triggering a cascade of problems.

What Did the Study Find About Long COVID and Brain Changes?

The research team, led by Dr. Yulin Ge and Dr. Thomas M. Wisniewski, studied 179 participants divided into three groups: 86 people with neurological symptoms of long COVID, 67 people who fully recovered from COVID-19 without lasting effects, and 26 healthy individuals who never had COVID-19. Using advanced MRI brain scans, blood tests, and cognitive exams, the researchers uncovered striking differences.

The findings were significant:

• Enlarged Brain Structure: Long COVID patients had a 10% larger choroid plexus compared to those who fully recovered from COVID-19 infection.
• Reduced Blood Flow: The enlarged choroid plexus also showed reduced blood flow through its vessels, suggesting impaired function and potential waste buildup in the brain.
• Alzheimer's-Linked Markers: The size increases in the choroid plexus tracked with elevated blood levels of proteins known to increase as Alzheimer's disease worsens, including pTau217, and with proteins that rise in response to brain injury, such as glial fibrillary acidic protein (GFAP).
• Cognitive Performance Decline: Patients with larger choroid plexuses performed an average of 2% worse on the mini-mental state examination (MMSE), a standard 30-point screening test that measures changes in memory and attention.

"Our work suggests that long-term immune reactions caused in some cases after an initial COVID infection may come with swelling that damages a critical brain barrier in the choroid plexus," said Dr. Ge, a professor in the Department of Radiology at NYU Grossman School of Medicine. "Physical, molecular, and clinical evidence suggests that a larger choroid plexus may be an early warning sign of future Alzheimer's-like cognitive decline".

How Could Long COVID Lead to Alzheimer's-Like Changes?

The researchers believe the mechanism involves inflammation-driven changes to the choroid plexus blood vessels. When immune cells remain activated for extended periods after COVID-19 infection, they trigger a process called "vascular remodeling," in which the layers of cells lining blood vessels thicken in response to ongoing immune signals. This thickening is accompanied by stromal fibrosis, the buildup of scar-like tissue that further restricts blood flow through the vessels.

This impaired blood flow has serious consequences. When the choroid plexus cannot function properly, it may struggle to produce adequate cerebrospinal fluid, allow harmful waste products to accumulate in the brain, and compromise the integrity of the blood-fluid barrier that normally protects brain tissue from harmful substances.

What Does This Mean for Long COVID Patients?

Long COVID, also called post-acute sequelae of COVID-19 (PASC), affects a substantial portion of the global population. Approximately 780 million people worldwide have been infected with the virus, and some experience long-term symptoms lasting months or even years after their initial infection. Common long COVID symptoms include persistent fatigue, brain fog, dizziness, loss of smell or taste, and depression.

The connection to Alzheimer's-like brain changes is particularly concerning because it suggests that some long COVID patients may face an elevated risk of cognitive decline later in life. However, researchers emphasize that more work is needed to understand whether these brain changes directly cause cognitive problems or are a consequence of other neurological symptoms.

"Our next step is to follow these patients over time to see if the brain changes we identified can predict who will develop long-term cognitive issues," explained Dr. Wisniewski, the Gerald J. and Dorothy R. Friedman Professor of the New York University Alzheimer's Disease Research Center. "A larger, long-term study will be needed to clarify whether these choroid plexus alterations are a cause or a consequence of the neurological symptoms, which promises to better focus treatment design efforts".

This research opens a new frontier in understanding how viral infections can have lasting effects on brain health and highlights the importance of monitoring long COVID patients for potential cognitive changes in the years ahead.