Related Experiment Videos
"Liquid Biopsy" of White Matter Hyperintensity in Functionally Normal Elders.
Fanny M Elahi1, Kaitlin B Casaletto1, Marie Altendahl1
1Memory and Aging Center, Department of Neurology, University of California, San Francisco, San Francisco, CA, United States.
Frontiers in Aging Neuroscience
|November 29, 2018
Summary
Endothelial-derived exosome proteins are elevated in older adults with white matter hyperintensities, indicating potential blood-brain barrier dysfunction. These findings link exosome cargo to cognitive decline and inflammation in aging brains.
Area of Science:
- Neuroscience
- Gerontology
- Biochemistry
Background:
- Aging is associated with increased blood-brain barrier (BBB) leakage and white matter hyperintensities (WMH), often attributed to small vessel disease or endotheliopathy.
- Investigating endothelial-derived exosomes (EDE) offers a novel in vivo approach to assess BBB integrity and associated pathologies.
Purpose of the Study:
- To quantify EDE protein cargo in neurologically normal older adults with and without WMH.
- To explore associations between EDE proteins, inflammation, and neurodegenerative changes.
Main Methods:
- A case-control study involving 26 neurologically normal older adults (11 with WMH, 15 without).
- Measurement of EDE proteins (GLUT1, LAT1, P-GP, NOSTRIN, VCAM1) via plasma exosome precipitation and enrichment.
- Assessment of inflammatory cytokines, cognitive function, and MRI-derived brain volumes.
Main Results:
- Significantly higher plasma levels of GLUT1, LAT1, P-GP, and NOSTRIN in subjects with WMH compared to controls.
- EDE proteins (GLUT1, LAT1, P-GP) effectively differentiated subjects with WMH (AUC 0.82-0.89).
- Elevated EDE proteins correlated with lower cognitive function, reduced gray matter volume, and higher IL-6 levels.
Conclusions:
- Concentrations of specific EDE proteins are significantly elevated in clinically normal older adults with WMH.
- This study provides in vivo evidence of molecular changes in brain endothelium associated with age-related white matter disease.