Amyloidosis is a protein conformational disorder with the distinctive feature of extracellular accumulation of amyloid fibrils that come from different proteins. In the ligamentum flavum of the lumbar spine, amyloid deposits were frequently found in elderly patients with lumbar spinal canal stenosis and were at least partially formed by wild-type transthyretin. However, how amyloid deposits in the ligamentum flavum affect lumbar spinal canal stenosis has remained unclear. In this study, we analyzed clinical, pathologic, and radiologic findings of patients with lumbar spinal canal stenosis who had amyloid deposits in the ligamentum flavum. We studied 95 ligamentum flavum specimens obtained from 56 patients with lumbar spinal canal stenosis and 21 ligamentum flavum specimens obtained from 19 patients with lumbar disk herniation. We evaluated histopathologic findings and clinicoradiologic manifestations, such as thickness of the ligamentum flavum and lumbar spinal segmental instability. We found that all 95 ligamentum flavum specimens resected from patients with lumbar spinal canal stenosis had amyloid deposits, which we classified into two types, transthyretin-positive and transthyretinnegative, and that transthyretin amyloid formation in the ligamentum flavum of patients with lumbar spinal canal stenosis was an age-associated phenomenon. The amount of amyloid in the ligamentum flavum was related to clinical manifestations of lumbar spinal canal stenosis, such as thickness of the ligamentum flavum and lumbar spinal segmental instability, in the patients with lumbar spinal canal stenosis with transthyretin-positive amyloid deposits. To our knowledge, this report is the first to show clinicopathologic correlations in transthyretin amyloid deposits of the ligamentum flavum. In conclusion, transthyretin amyloid deposits in the ligamentum flavum may be related to the pathogenesis of lumbar spinal canal stenosis in elderly patients.

Senile systemic amyloidosis is a common age-related amyloidosis that involves accumulation of wild-type transthyretin, with cardiac dysfunction being a predominant result. The importance of obtaining an accurate diagnosis of senile systemic amyloidosis has been increasingly recognized, so that novel treatments are being developed. However, the clinicopathological features of senile systemic amyloidosis remain to be completely understood. Here, we evaluated cardiac specimens from 181 consecutive post-mortem cases older than 40 years, including 6 cases of senile systemic amyloidosis, and 5 cases of familial amyloidotic polyneuropathy, which is a hereditary systemic amyloidosis caused by mutant forms of transthyretin. Furthermore, we studied ante-mortem clinicopathological findings of 11 senile systemic amyloidosis cases, in which 9 cases underwent gastrointestinal tract biopsy and/or subcutaneous tissue biopsy, at Kumamoto University Hospital. Of the autopsied cases of elderly Japanese (older than 80 years), 12% had senile systemic amyloidosis, with the percentage increasing with age. The occurrence of senile systemic amyloidosis in elderly Japanese patients was lower than that in previous reports, which suggests that a genetic background and/or environmental factor(s) may have important roles in the occurrence of senile systemic amyloidosis. Transthyretin amyloid deposits in familial amyloidotic polyneuropathy cases developed mainly in the pericardium and the surrounding muscle fascicles, whereas in cases with senile systemic amyloidosis the transthyretin amyloid deposits had a patchy plaque-like shape and developed mainly inside the ventricular wall. Biopsies from senile systemic amyloidosis patients evidenced amyloid deposits in 44% (4/9) of gastrointestinal tract and subcutaneous tissue samples combined. As myocardial biopsy may be dangerous for elderly people, the use of a combination of gastrointestinal tract and subcutaneous tissue biopsies may make diagnosis of senile systemic amyloidosis easier.

FAP may shift to systemic WT TTR amyloid formation after LT, which seems to be similar to the process in SSA. The truncation of TTR in amyloid deposits may depend on some genetic or environmental factors other than undergoing LT.

Domino liver transplantation (DLT) with liver grafts from patients with hereditary transthyretin (TTR) amyloidosis has been performed throughout the world because of a severe liver graft shortage. Reports of acquired systemic TTR amyloidosis in domino liver recipients have been increasing; however, the precise pathogenesis and clinical course of acquired TTR amyloidosis remains unclear. We analyzed the relationship between the occurrence of acquired amyloidosis and clinical features in 22 consecutive domino liver donors with hereditary TTR amyloidosis (10 males and 12 females; mean age at DLT: 37.2 years; TTR mutations: V30M [n 5 19], Y114C [n 5 1], L55P [n 5 1], and S50I [n 5 1]) and 22 liver recipients (16 males and 6 females; mean age at DLT, 46.2 years). The mean times from DLT to amyloid first appearance and transplant recipient symptom onset were 8.2 years and 9.9 years, respectively. Kaplan-Meier analysis and quantification of the amyloid deposition revealed aging of recipients correlated with early de novo amyloid deposition. The sex of donors and recipients and the age, disease duration, and disease severity of donors had no significant effect on the latency of de novo amyloid deposition. In conclusion, our results demonstrate that recipient aging is associated with the early onset de novo amyloidosis. Because acquired amyloidosis will likely increase, careful follow-up for early amyloidosis detection and new treatments, including TTR stabilizers and gene-silencing therapies, are required.

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