Transthyretin Amyloidosis as a Cause of Lumbar Spinal Stenosis

Transthyretin (TTR) amyloidosis, also known as senile systemic amyloidosis, occurs as a misfolded form of transthyretin forms solid deposits in tissues. In young people this is only threatening when accompanied by rare genetic mutations that greatly accelerate the process, but ongoing accumulation of this amyloid throughout life happens to everyone. If you live to a very great age and survive all of the other forms of age-related disease, then this amyloid will grow to clog your cardiovascular system and kill you. Safe removal of this transthyretin amyloid must thus be a part of any future rejuvenation treatment, and so the SENS Research Foundation funds some lines of research, such as work on catabodies that can break down amyloid deposits. Unfortunately this is in general a small, poorly funded area of research - few groups are looking into TTR amyloidosis, which is why non-profits like the Foundation are trying to hurry matters along.

In this open access paper researchers suggest that in earlier old age TTR amyloid causes other issues, in particular a painful form of degeneration known as lumber spinal stenosis - though more work than was accomplished here would be needed for proof. Producing treatments for this manifestation of amyloidosis would probably be more of a motivation for developers to work on ways to remove amyloid, as there are more patients and thus greater potential revenue from a therapy. So it goes:

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 a clinical syndrome of usually elderly individuals that depends on narrowing of the lumbar spinal canal. It is characterized by compression of sensory and motoric nerves to the lower limbs, leading to an often disabling condition. The pathogenesis is probably heterogeneous but includes disc degeneration with disc height decrease and secondary facet-joint subluxation leading to osteoarthritis. Also a degenerative spondylolisthesis of the affected spinal segment may be involved in most cases. Other central factors are general degenerative processes in cartilage and ligaments, including ligamentum flavum.

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



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