Apolipoprotein AI amyloid deposits in the ligamentum flavum in patients with lumbar spinal canal stenosis

Abstract

Amyloidosis is a protein-misfolding disease characterised by insoluble amyloid deposits in the extracellular space of various organs and tissues, such as the brain, heart, kidneys, and ligaments. We previously reported the frequent occurrence of amyloid deposits in the ligament flavum in the presence of lumbar spinal canal stenosis (LSCS), which is a common spinal disorder in older individuals. Our earlier clinicopathological studies revealed that amyloid deposits derived from transthyretin (TTR) were involved in the pathogenesis of LSCS. ATTR amyloid was the most common form in the ligamentum flavum, but amyloid deposits that were not identified still existed in more than 50% of patients with LSCS. In this study, we found apolipoprotein AI (AApoAI) amyloid deposits in the ligamentum flavum of patients with LSCS. The deposits occurred in 12% of patients with LSCS. Biochemical studies revealed that the amyloid deposits consisted mainly of full-length ApoAI. As a notable finding, the lumbar ligamentum flavum of patients who had LSCS with double-positive amyloid deposits—positive for both ATTR and AApoAI—was significantly thicker than that of patients who had LSCS with single-positive—that is, positive for either ATTR or AApoAI—amyloid deposits. We thus suggest that lumbar AApoAI amyloid formation may enhance the pathological changes of lumbar ATTR amyloidosis in patients with LSCS.

Keywords:

• Amyloidosis
• apolipoprotein AI
• lumbar spinal canal stenosis
• transthyretin

Acknowledgments

We thank Ms. Hiroko Katsura for technical assistance and Ms. Judith B. Gandy for providing professional English editing of the manuscript.

Disclosure statement

No potential conflict of interest was reported by the author(s).

Additional information

Funding

This work was supported by JSPS KAKENHI Grant Numbers 17K08987 and 26860372.