Wild-type transthyretin-derived amyloidosis in various ligaments and tendons

Sueyoshi, Tetsuro; Ueda, Mitsuharu; Jono, Hirofumi; Irie, Hiroki; Sei, Akira; Ide, Junji; Ando, Yumiko; Mizuta, Hiroshi

doi:10.1016/j.humpath.2010.11.017

Cited by 118 publications

(88 citation statements)

References 33 publications

(43 reference statements)

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“…These features of transthyretin amyloid deposits in the ligamentum flavum were consistent with a few previous reports that evaluated smaller numbers of lumbar spinal canal stenosis patients. 13,14,22 In addition, because we discovered no relationship between the amount of transthyretin amyloid and age, we speculate that aging mainly affects the initiation of transthyretin amyloid formation in the ligamentum flavum. Because we found no symptoms that would indicate cardiac amyloidosis, which is major symptom of senile systemic amyloidosis, an age-related systemic form of amyloidosis, transthyretin-positive amyloid deposition in the ligamentum flavum of lumbar spinal canal stenosis patients may be a localized form of amyloidosis.…”

Section: Discussionmentioning

confidence: 82%

“…11,12 We recently reported that amyloid deposits in the ligamentum flavum were at least partially derived from wild-type transthyretin in elderly lumbar spinal canal stenosis patients. 13 Another recent paper suggested that transthyretin amyloid formation may be a common cause of lumbar spinal canal stenosis. 14 We also reported that a senile systemic amyloidosis patient with multifocal spinal transthyretin amyloid deposits developed severe destructive spondylosis and radiculomyelopathy.…”

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confidence: 99%

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Amyloid deposits derived from transthyretin in the ligamentum flavum as related to lumbar spinal canal stenosis

et al. 2015

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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.

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Section: Discussionmentioning

confidence: 82%

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confidence: 99%

Amyloid deposits derived from transthyretin in the ligamentum flavum as related to lumbar spinal canal stenosis

et al. 2015

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“…We recently demonstrated wild-type transthyretinderived amyloid deposits in 35% (39/111 cases) of surgically resected ligaments from patients older than 40 years with orthopedic disorders. 23 Amyloid deposits in such ligaments of senile systemic amyloidosis patients may frequently develop without obvious symptoms. On the basis of those findings, we speculate that aging of the tissue matrix caused by long-term mechanical stress may have an important role in amyloid formation in senile systemic amyloidosis.…”

Section: Discussionmentioning

confidence: 99%

Clinicopathological features of senile systemic amyloidosis: an ante- and post-mortem study

et al. 2011

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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.

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“…B. Lig. carpi transversum; [39,40]). In Autopsiestudien wird bei über 85-jährigen Personen eine Prävalenz der ATTR-Amyloidose von ungefähr 25% angegeben.…”

Section: Kardiale Beteiligungunclassified

Amyloidose des Herzens

Kristen

Röcken

2012

Pathologe

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Amyloidosis is a heterogeneous group of diseases characterized by the pathological deposition of autologous proteins in an antiparallel β-sheet confirmation forming non-branching linear fibrils of indefinite length and an approximate diameter of 10-12 nm. Cardiac amyloidosis is caused by deposits in the heart and may lead to cardiac arrhythmia and low output failure. Following the diagnosis, classification of the amyloid protein and evaluation of further organ involvement is mandatory. Treatment approaches are based on reduction of the production of amyloid precursor proteins. Standard heart failure treatment is usually not well tolerated and the underlying disease remains unaffected. Cardiac amyloidosis, especially of the light chain type, is associated with a poor outcome. The clinical picture is uncharacteristic, therefore correct diagnosis of cardiac amyloidosis is often delayed in many patients. Combination of clinical symptoms of different organ systems should alert the physician to the diagnosis of amyloidosis.

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Wild-type transthyretin-derived amyloidosis in various ligaments and tendons

Cited by 118 publications

References 33 publications

Amyloid deposits derived from transthyretin in the ligamentum flavum as related to lumbar spinal canal stenosis

Amyloid deposits derived from transthyretin in the ligamentum flavum as related to lumbar spinal canal stenosis

Clinicopathological features of senile systemic amyloidosis: an ante- and post-mortem study

Amyloidose des Herzens

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