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Brains of COVID-19 patients had some of the same pathological changes seen in Alzheimer's disease, which may explain the memory problems people with long COVID experience, a small study suggested.

The study, based on autopsies of 10 people who died with COVID-19, linked the inflammatory response found in SARS-CoV-2 infection with pathways causing tau hyperphosphorylation typically associated with Alzheimer's disease, reported Andrew Marks, MD, of Columbia University in New York City, and co-authors.

The data also indicated a role for leaky ryanodine receptor 2 (RyR2) in the pathophysiology of SARS-CoV-2 infection, the researchers wrote in .

"The study shows that long COVID-19 brain fog may be a form of Alzheimer's disease, but much more research needs to be done before we can make more definitive conclusions," Marks told 番茄社区app.

"The major strength of the paper is that they identified abnormalities in several molecules which help characterize the neuroglial dysfunction in these patients at a biochemical level," noted Avindra Nath, MD, of the National Institute of Neurological Disorders and Stroke in Bethesda, Maryland, who wasn't involved with the study.

"However no histology was performed for Alzheimer's type pathology and the implications for development of Alzheimer's disease would be hard to extrapolate from this study," Nath pointed out.

Defective ryanodine receptors have been implicated in diverse processes, including and lung disease. , they previously have been linked to an increase in phosphorylated tau.

Persistent brain fog and cardiac symptoms in people with COVID-19 led Marks and co-authors to investigate how ryanodine receptors were affected in COVID-19. "What we found is really, I think, quite unexpected," Marks said. "Not only did we find defective ryanodine receptors in the hearts and lungs of deceased COVID patients, we also found them in their brains."

The researchers analyzed signaling molecules in brain lysates of COVID-19 patients and controls and found evidence linking SARS-CoV-2 infection to activation of TGF-β signaling and oxidative overload. They also found high levels of phosphorylated tau in COVID-19 patients' brains, both in areas where tau is typically located in Alzheimer's and in other sites. No changes in pathways leading to amyloid beta formation were seen.

The findings may mean that a COVID-19 immune response causes brain inflammation which leads to dysfunctional ryanodine receptors and altered cellular calcium dynamics, then to increases in phosphorylated tau, Marks and colleagues noted. "We propose a potential mechanism that may contribute to the neurological complications caused by SARS-CoV-2: defective intracellular Ca²⁺ regulation and activation of Alzheimer's disease-like neuropathology," they wrote.

Leaky RyR2 channels may be a therapeutic target to ameliorate some of the cognitive defects associated with SARS-CoV-2 infection and long COVID, the researchers suggested.

Lab studies that treated COVID-19 patient brain samples with a drug targeting RyR2 channels prevented the calcium leak. The treatment, known as ARM210, currently is undergoing at NIH for RyR1-related myopathy.

"Future experiments will explore calcium channels as a potential therapeutic target for the neurological complications associated with COVID-19," Marks and co-authors wrote.

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