Transthyretin Amyloid Neuropathy: The Schwann Cell Hypothesis

Murakami, Tatsufumi; Sunada, Yoshihide

doi:10.1007/978-981-32-9636-7_24

Cited by 7 publications

(9 citation statements)

References 35 publications

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“…In these cases, demyelinating findings were probably secondary to axonal loss, rather than caused by direct damage to the myelin, as frequently observed in other neuropathies [22,23]. However, since TTR is expressed in Schwann cells, a direct toxic effect on these cells, and on the nearby dorsal root ganglia, cannot be excluded [24,25]. There is progressive evidence that the oligomers of amyloidogenic proteins play a key role in mediating toxicity in other common neurodegenerative diseases, including Alzheimer's disease and Parkinson's disease [26].…”

Section: Discussionmentioning

confidence: 63%

hATTR Pathology: Nerve Biopsy Results from Italian Referral Centers

et al. 2020

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Pathological evidence of amyloid on nerve biopsy has been the gold standard for diagnosis in hereditary transthyretin amyloidosis polyneuropathy (hATTR-PN) for a long time. In this article, we reviewed the pathological findings of a large series of sural nerve biopsies from a cohort of hATTR-PN patients, collected by different Italian referral centers. Patients and Methods: We reviewed clinical and pathological data from hATTR-PN patients, diagnosed and followed in five Italian referral centers for peripheral neuropathies. Diagnosis was formulated after a positive genetic test for transthyretin (TTR) mutations. Sural nerve biopsy was performed according to standard protocols. Results: Sixty-nine sural nerve biopsies from hATTR-PN patients were examined. Congo red positive deposits were found in 73% of cases. Only the Phe64Leu mutation failed to show amyloid deposits in a high percentage of biopsies (54%), as already described. Unusual pathological findings, such as myelin abnormalities or inflammatory infiltrates, were detected in occasional cases. Conclusions: Even if no longer indicated to confirm hATTR-PN clinical suspicion, nerve biopsy remains, in expert hands, a rapid and inexpensive tool to detect amyloid deposition. In Italy, clinicians should be aware that a negative biopsy does not exclude hATTR-PN, particularly for Phe64Leu, one of the most frequent mutations in this country.

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Section: Discussionmentioning

confidence: 63%

hATTR Pathology: Nerve Biopsy Results from Italian Referral Centers

et al. 2020

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“…1,6,11,[24][25][26][27][28] Lastly, other mechanisms could be taken into account such as nerve ischemia caused by perivascular amyloids, 26 inefficient cleavage of TTR aggregates 29 and dysfunction of SCs and glial cells. 30…”

Section: Neurodegenerative Mechanismsmentioning

confidence: 99%

The neuropathy in hereditary transthyretin amyloidosis: A narrative review

Tozza

Severi

Spina

et al. 2021

J Peripheral Nervous Sys

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Hereditary transthyretin amyloidosis (ATTRv) is a condition with adult onset, caused by mutation of the transthyretin (TTR) gene and characterized by extracellular deposition of amyloid fibrils in tissue, especially in the peripheral nervous system (PNS) and heart. PNS involvement leads to a rapidly progressive and disabling sensory-motor axonal neuropathy. Although awareness among neurologists increased in recent years thanks to new treatment options, ATTRv is frequently misdiagnosed, and thus a correct diagnosis can be delayed by several years. This review aims to draw the history and features of polyneuropathy in ATTRv based on pathological and electrophysiological correlates. We assessed original articles and case reports based on their relevance to ATTRv neuropathy and we included those appropriate for the scheme of this narrative review. Amyloid fibrils initially deposit in ganglia, causing an axonal neuropathy without amyloid deposits in distal segments (eg, sural nerve biopsy). Over time, amyloid fibrils spread along the nerves, leading to some demyelinating features in the context of severe axonal loss. This review highlights how the features of neuropathy change based on type of ATTRv (early vs late onset) and stage of disease.

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“…With disease progression, large-myelinated fibers are also affected and loss of motor neurons even occurs in some of these diseases [ 40 ]. In addition to peripheral sensory nerves and DRGs [ 74 , 90 , 91 ], amyloid has also been detected in autonomic nerves [ 92 ] and autonomic ganglia [ 21 ]. As a consequence, autonomic dysfunction is present in several of the amyloid diseases ( Table 1 and [ 83 ]).…”

Section: Peripheral Amyloid Neuropathiesmentioning

confidence: 99%

“…A phenomenon that is often observed in familial amyloid neuropathy is defective myelination [ 91 , 307 , 308 ]. As such, impairment in Schwann cell function is emerging as an important mechanism in the development of amyloid neuropathy or neuropathic pain in general [ 309 ].…”

Section: Mechanisms Linking Amyloid and Peripheral Neuropathymentioning

confidence: 99%

“…In addition, conditioned medium of these TTRv Schwann cells inhibited sensory neuron neurite outgrowth [ 311 ]. Thus, TTR gene expression in Schwann cells might contribute to neurodegeneration in FAP [ 91 ]. Schwann cells also produce SAA, the expression of which is upregulated by IL-6 and corticosteroids [ 312 ].…”

Section: Mechanisms Linking Amyloid and Peripheral Neuropathymentioning

confidence: 99%

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Amyloid Proteins and Peripheral Neuropathy

Asiri

Engelsman

Eijkelkamp

et al. 2020

Cells

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Painful peripheral neuropathy affects millions of people worldwide. Peripheral neuropathy develops in patients with various diseases, including rare familial or acquired amyloid polyneuropathies, as well as some common diseases, including type 2 diabetes mellitus and several chronic inflammatory diseases. Intriguingly, these diseases share a histopathological feature—deposits of amyloid-forming proteins in tissues. Amyloid-forming proteins may cause tissue dysregulation and damage, including damage to nerves, and may be a common cause of neuropathy in these, and potentially other, diseases. Here, we will discuss how amyloid proteins contribute to peripheral neuropathy by reviewing the current understanding of pathogenic mechanisms in known inherited and acquired (usually rare) amyloid neuropathies. In addition, we will discuss the potential role of amyloid proteins in peripheral neuropathy in some common diseases, which are not (yet) considered as amyloid neuropathies. We conclude that there are many similarities in the molecular and cell biological defects caused by aggregation of the various amyloid proteins in these different diseases and propose a common pathogenic pathway for “peripheral amyloid neuropathies”.

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Transthyretin Amyloid Neuropathy: The Schwann Cell Hypothesis

Cited by 7 publications

References 35 publications

hATTR Pathology: Nerve Biopsy Results from Italian Referral Centers

hATTR Pathology: Nerve Biopsy Results from Italian Referral Centers

The neuropathy in hereditary transthyretin amyloidosis: A narrative review

Amyloid Proteins and Peripheral Neuropathy

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