Exposure to Low-Intensity Blast Increases Clearance of Brain Amyloid Beta.

Abstract

The long-term effects of exposure to blast overpressure are an important health concern in military personnel. Increase in amyloid beta (Aβ) has been documented after non-blast traumatic brain injury (TBI) and may contribute to neuropathology and an increased risk for Alzheimer's disease. We have shown that Aβ levels decrease following exposure to a low-intensity blast overpressure event. To further explore this observation, we examined the effects of a single 37 kPa (5.4 psi) blast exposure on brain Aβ levels, production, and clearance mechanisms in the acute (24 h) and delayed (28 days) phases post-blast exposure in an experimental rat model. Aβ and, notably, the highly neurotoxic detergent soluble Aβ42 form, was reduced at 24 h but not 28 days after blast exposure. This reduction was not associated with changes in the levels of Aβ oligomers, expression levels of amyloid precursor protein (APP), or increase in enzymes involved in the amyloidogenic cleavage of APP, the β- and ϒ-secretases BACE1 and presenilin-1, respectively. The levels of ADAM17 α-secretase (also known as tumor necrosis factor α-converting enzyme) decreased, concomitant with the reduction in brain Aβ. Additionally, significant increases in brain levels of the endothelial transporter, low-density related protein 1 (LRP1), and enhancement in co-localization of aquaporin-4 (AQP4) to perivascular astrocytic end-feet were observed 24 h after blast exposure. These findings suggest that exposure to low-intensity blast may enhance endothelial clearance of Aβ by LRP1-mediated transcytosis and alter AQP4-aided glymphatic clearance. Collectively, the data demonstrate that low-intensity blast alters enzymatic, transvascular, and perivascular clearance of Aβ.

• Authors: Rania Abutarboush, Eileen Reed, Ye Chen, Ming Gu, Cameron Watson, Usmah Kawoos, Jonathan K Statz, Anna E Tschiffely, Stephanie Ciarlone, Georgina Perez-Garcia, Miguel A Gama Sosa, Rita de Gasperi, James R Stone, Gregory A Elder, Stephen T Ahlers
• Journal: Journal of neurotrauma (J Neurotrauma) Vol. 41 Issue 5-6 Pg. 685-704 (03 2024) ISSN: 1557-9042 [Electronic] United States
• PMID: 38183627 (Publication Type: Journal Article, Research Support, U.S. Gov't, Non-P.H.S.)

Chemical References

• Amyloid beta-Peptides
• Amyloid Precursor Protein Secretases
• Aspartic Acid Endopeptidases
• Amyloid beta-Protein Precursor
• Aquaporin 4

Topics

• Animals
• Rats
• Amyloid beta-Peptides
• Amyloid Precursor Protein Secretases
• Aspartic Acid Endopeptidases
• Brain
• Amyloid beta-Protein Precursor
• Aquaporin 4