High altitude is associated with pTau deposition, neuroinflammation, and myelin loss

• Published in: Scientific reports 2022-04, Vol.12 (1), p.6839-6839, Article 6839
• Main Authors: Iacono, Diego, Murphy, Erin K., Sherman, Paul M., Chapapas, Holly, Cerqueira, Bianca, Christensen, Christine, Perl, Daniel P., Sladky, John
• Format: Article
• Language: English
• Subjects: 631/378; 631/378/87; Acclimation; Acclimatization; Altitude; Animals; Brain - diagnostic imaging; Brain - pathology; Cerebellum; High-altitude environments; Hippocampus; Humanities and Social Sciences; Hypoxia; Immunohistochemistry; Inflammation; Magnetic Resonance Imaging; Mammals; multidisciplinary; Myelin basic protein; Myelin Sheath; Myelination; Neuroinflammatory Diseases; Pilots; Science; Science (multidisciplinary); Sea level; Substantia alba; Swine; Tau protein; Western blotting
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/s41598-022-10881-x

Mammals are able to adapt to high altitude (HA) if appropriate acclimation occurs. However, specific occupations (professional climbers, pilots, astronauts and other) can be exposed to HA without acclimation and be at a higher risk of brain consequences. In particular, US Air Force U2-pilots have been shown to develop white matter hyperintensities (WMH) on MRI. Whether WMH are due to hypoxia or hypobaria effects is not understood. We compared swine brains exposed to 5000 feet (1524 m) above sea level (SL) with 21% fraction inspired O 2 (FiO 2 ) (Control group [C]; n = 5) vs. 30,000 feet (9144 m) above SL with 100% FiO 2 group (hypobaric group [HYPOBAR]; n = 6). We performed neuropathologic assessments, molecular analyses, immunohistochemistry (IHC), Western Blotting (WB), and stereology analyses to detect differences between HYPOBAR vs. Controls. Increased neuronal insoluble hyperphosphorylated-Tau (pTau) accumulation was observed across different brain regions, at histological level, in the HYPOBAR vs. Controls. Stereology-based cell counting demonstrated a significant difference ( p