Transthyretin-derived amyloidosis: probably a common cause of lumbar spinal stenosis

Abstract

Background: Senile systemic amyloidosis (SSA) derived from wild-type transthyretin is a fairly common condition of old individuals, particularly men. The main presentation is by cardiac involvement, which can lead to severe restrictive cardiomyopathy. SSA is, however, a systemic disease, and amyloid deposits may appear in many other tissues but are thought to be without clinical symptoms outside the heart. Amyloid is a very common finding in cartilage and ligaments of elderly subjects, and transthyretin has been demonstrated in some deposits. Lumbar spinal stenosis is also a condition of usually elderly individuals in whom narrowing of the lumbar spinal canal leads to compression of nerves to the lower limbs.

Results: We questioned whether lumbar spinal stenosis sometimes could be a manifestation of undiagnosed SSA. In this first report we have studied the presence of amyloid in material obtained at surgery for spinal stenosis in 26 patients. Amyloid was found in 25 subjects. Transthyretin was demonstrated immunohistochemically in 5 out of 15 studied resected tissues. Four of the positive materials were analyzed with Western blot revealing both full-length transthyretin (TTR) and C-terminal TTR fragments, typically seen in SSA.

Conclusion: We conclude that lumbar spinal stenosis quite frequently may be a consequence of SSA and that further studies are warranted.

Keywords: apolipoprotein A-I; lumbar spinal stenosis; senile systemic amyloidosis; transthyretin.

Figures

Figure 1.

Section of ligament with amyloid deposits immunolabeled for transthyretin and stained with Congo red. Overlapping of immunoreaction with Congo red positivity is evident. Polarized light with partially crossed polars. Bar 200 µm.

Figure 2.

Electron micrograph of ligament with transthyretin-amyloid deposits (A) with typical fine fibrillar appearance, intermingled with collagen fibers (Co). The section was immunolabeled for transthyretin and reaction visualized with 10 nm gold particles. Bar 500 nm.

Figure 3.

Adjacent sections of ligament immunolabeled for transthyretin (A) and apoA-I (B). While immunolabeling for transthyretin is homogeneous, that for apoA-I is more spotty. Bar 200 µm.

Figure 4.

Western blot analysis of extracts of two spinal stenosis materials, positive for transthyretin at immunohistochemistry. Included is also an extract of amyloid fibrils obtained from the heart of a patient with senile systemic amyloidosis. The pattern is the same in all three materials with full-length transthyretin as well as a prominent band corresponding to C-terminal fragments. The unlabeled band between monomers and dimers has constantly been found in senile systemic amyloidosis and may be dimers of fragments.