Detection of ATTR aggregates in plasma of polyneuropathic ATTR-V30M amyloidosis patients DOI Creative Commons
Rose Pedretti, Lanie Wang, Justin L. Grodin

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: May 13, 2024

Abstract ATTR amyloidosis is caused by the deposition of transthyretin amyloid fibrils in tissues often leading to organ failure and death. The clinical spectrum this disease highly diverse dependent on many factors including presence or absence mutations within protein and/or an individual’s ancestry. phenotypic variability makes it difficult diagnose, delaying treatment worsening patient prognosis. Our lab has recently developed a peptide probe that detects aggregates plasma patients with cardiomyopathy but not been tested from polyneuropathic patients. Here we evaluate our cohort Portuguese carrying ATTR-V30M mutation having no cardiac phenotype. We found could indeed detect their plasma, there appeared be relationship between age gender. work broad implications pathobiology contribute validation as novel detection tool for disease.

Language: Английский

ATTRv-V30M amyloid fibrils from heart and nerves exhibit structural homogeneity DOI
Binh A. Nguyen, Shumaila Afrin, Anna Yakubovska

et al.

Structure, Journal Year: 2024, Volume and Issue: 32(12), P. 2244 - 2250.e3

Published: Oct. 17, 2024

Language: Английский

Citations

2
ATTRv-V30M Type A amyloid fibrils from the heart and nerves exhibit structural homogeneity. DOI Creative Commons
Binh A. Nguyen, Shumaila Afrin, Anna Yakubovska

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: May 14, 2024

ATTR amyloidosis is a systemic disease characterized by the deposition of amyloid fibrils made transthyretin, protein integral to transporting retinol and thyroid hormones. Transthyretin primarily produced liver circulates in blood as tetramer. The retinal epithelium also secretes which secreted vitreous humor eye. Because mutations or aging, transthyretin can dissociate into amyloidogenic monomers triggering fibril formation. myocardium peripheral nerves causes cardiomyopathies neuropathies, respectively. Using cryo-electron microscopy, here we determined structures extracted from cardiac nerve tissues an ATTRv-V30M patient. We found that both share consistent structural conformation, similar previously described structure individual with same genotype, but different obtained humor. Our study hints uniform fibrillar architecture across within individual, only when source liver. Moreover, this provides first description patient enhances our understanding role site production shaping amyloidosis.

Language: Английский

Citations

1
Detection of ATTR aggregates in plasma of polyneuropathic ATTR-V30M amyloidosis patients DOI Creative Commons
Rose Pedretti, Lanie Wang, Justin L. Grodin

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: May 13, 2024

Abstract ATTR amyloidosis is caused by the deposition of transthyretin amyloid fibrils in tissues often leading to organ failure and death. The clinical spectrum this disease highly diverse dependent on many factors including presence or absence mutations within protein and/or an individual’s ancestry. phenotypic variability makes it difficult diagnose, delaying treatment worsening patient prognosis. Our lab has recently developed a peptide probe that detects aggregates plasma patients with cardiomyopathy but not been tested from polyneuropathic patients. Here we evaluate our cohort Portuguese carrying ATTR-V30M mutation having no cardiac phenotype. We found could indeed detect their plasma, there appeared be relationship between age gender. work broad implications pathobiology contribute validation as novel detection tool for disease.

Language: Английский

Citations

0