Nelson awarded $2.68 million NIH grant to study impact of pneumonia on the brain

Multiphon image taken by Amy R. Nelson, Ph.D., of blood

vessels (white) and pericyte cell bodies (pink) in a healthy

brain, as published in Alzheimer's & Dementia.

With a $2.68 million grant from the National Institute of Neurological Disorders and Stroke, scientists at the University of South Alabama aim to understand the impact of pneumonia on the brain.

Amy R. Nelson, Ph.D., an associate professor of physiology and cell biology at the Frederick P. Whiddon College of Medicine, is principal investigator of the project, which brings together experts in brain and lung biology. The study is funded by the National Institutes of Health’s Research Project Grant Program (R01) over a five-year period.

Postoperative pneumonia, also known as hospital-acquired pneumonia, occurs in about 2% to 8% of patients following surgery and increases the length of hospital stay and mortality. Some pneumonia survivors, including those with post-intensive care unit syndrome, experience cognitive deficits, reducing their quality of life and causing healthcare and financial hardships. 

Pneumonia-associated microorganisms, such as P. aeruginosa bacteria, trigger lung endothelial production and the release of several cytotoxic amyloids, including tau, that are key pathological hallmarks of Alzheimer’s disease. Amyloids are proteins that can build up in tissues and organs and disrupt their function.

Mike Lin, Ph.D., a professor of physiology and cell biology, and his collaborators previously reported that cytotoxic tau produced by lung endothelial cells in response to bacterial pneumonia infection accumulates in the brain, resulting in impaired learning and memory. Lin is also a co-investigator on this new project.

“The main focus of this study is whether cytotoxic tau from the lungs impacts cells supporting brain blood vessels,” Nelson said. “We will also determine the impact of the greatest genetic risk factor for sporadic Alzheimer’s disease, apolipoprotein E4, on brain injury during pneumonia. Previous studies have shown that apolipoprotein E4 carriers had a greater prevalence of dying from COVID-19. The link between apolipoprotein E4 and pneumonia is an understudied new direction that perhaps may explain why E4 carriers have an increased risk of sporadic Alzheimer’s disease.” 

This is a preclinical, translational study using experimental models, clinical samples, and post-mortem tissues to determine human relevance, Nelson said.

Contributors to the project from the University of South Alabama include Lin; Mikhail Alexeyev, Ph.D., associate professor of physiology and cell biology; Ron Balczon, Ph.D., professor of biochemistry and molecular biology; Osama Elkadi, M.D., associate professor of pathology; and Troy Stevens, Ph.D., professor and chair of physiology and cell biology. 

Image source: Silva NCBS, Bracko O, Nelson AR, et al. Vascular cognitive impairment and dementia: An early career researcher perspective. Alzheimers Dement (Amst). 2022;14(1):e12310. Published 2022 Apr 27. doi:10.1002/dad2.12310