Dimitrios Kapogiannis: Messages in Neural Nanobubbles: Extracellular Vesicles and Brain Disorders

BRAIN PONDERINGS

All cells including neurons in the brain release tiny (~ 100 nanometers in diameter) bubble-like vesicles that contain various molecules produced by the cell. These extracellular vesicles (EVs) are thought to have a variety of functions including sending molecular messages between cells and removing molecular garbage from the cells. Some EVs released from cells throughout the body and brain make their way into the bloodstream. Dimitrios Kapogiannis at the National Institute on Aging Biomedical Research Center in Baltimore, developed a technology for isolating EVs produced by neurons from the blood. By measuring amounts of abnormal Tau protein in neuronal EVs from patients with Alzheimer’s disease (AD) and controls, and in longitudinal studies of people in the years preceding their cognitive impairment, he showed that his test can identify people who will very likely become symptomatic. It turns out that neuronal EVs have insulin receptors in their membrane and Dimitrios provided evidence that neuronal EVs from AD patients exhibit insulin resistance. Because intermittent fasting can increase the sensitivity of cells to insulin and is effective in countering the disease process in AD mouse models, Dimitrios performed a clinical trials of intermittent fasting in older individuals with insulin resistance and found that it improved their performance on several memory tests. More recently he headed a clinical trial of a ketone ester in patients in older people at risk for AD. This episode is all about EVs – where they come from, the kinds of molecules they contain, their normal functions, and changes in EVs in Alzheimer’s disease (AD) and other brain disorders that can be used for diagnosis and in clinical trials.

LINKS

Dr. Kapogiannis’ NIA webpage: https://www.nia.nih.gov/about/staff/kapogiannis-dimitrios

Review articles on EVs:

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5439289/

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9985115/pdf/nihms-1878107.pdf

Key publications:

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4314222/?report=printable

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6632160/?report=printable

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8146429/pdf/cells-10-00993.pdf

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10060702/pdf/awac258.pdf