Researchers at the New York-based NYU Langone Health report that structural changes in the brains of patients with Long COVID are associated with blood biomarkers tied to Alzheimer’s disease and with modest declines in cognitive performance.

The study, published Feb. 10 in Alzheimer’s & Dementia, focuses on the choroid plexus, a network of blood vessels that produces cerebrospinal fluid and helps regulate immune activity and waste clearance in the brain. Prior research has shown that SARS-CoV-2 can damage cells lining these vessels.

In an analysis of 179 participants, investigators compared 86 patients with neurological symptoms of Long COVID, 67 people who had recovered from COVID-19 without lasting symptoms and 26 individuals who had never been infected. All participants underwent advanced MR scans, blood testing and cognitive assessment.
Patients with Long COVID had a choroid plexus volume about 10% larger than those who had fully recovered. Larger size was associated with higher blood levels of pTau217, a protein linked to Alzheimer’s progression, and glial fibrillary acidic protein, a marker of brain injury. Participants with enlarged choroid plexuses also scored an average of 2% lower on the 30-point Mini-Mental State Exam.

“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 senior study author Dr. Yulin Ge, a professor in the department of radiology at the NYU Grossman School of Medicine. “Physical, molecular, and clinical evidence suggests that a larger CP may be an early warning sign of future Alzheimer's-like cognitive decline.”

Imaging also indicated reduced blood flow in the affected structure. The authors propose that chronic inflammation may lead to vascular remodeling and fibrosis, potentially impairing cerebrospinal fluid production and barrier integrity.

“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,” said senior study author Thomas Wisniewski, M.D., the Gerald J. and Dorothy R. Friedman Professor in the department of neurology at the NYU Grossman School of Medicine.

The work was supported by grants from the National Institute on Aging.

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