Review
Clinical Neurology
Loris Poli, Beatrice Labella, Stefano Cotti Piccinelli, Filomena Caria, Barbara Risi, Simona Damioli, Alessandro Padovani, Massimiliano Filosto
Summary: Amyloidoses are a group of diseases characterized by the accumulation of insoluble misfolded protein material called amyloid. Transthyretin amyloidosis (ATTR) is a subtype related to abnormalities in the transthyretin protein. It can be hereditary or occur spontaneously, and affects multiple vital organs. Timely diagnosis is crucial due to the availability of effective treatments.
FRONTIERS IN NEUROLOGY
(2023)
Article
Clinical Neurology
Luca Leonardi, Clovis Adam, Guillemette Beaudonnet, Diane Beauvais, Cecile Cauquil, Adeline Not, Olivier Morassi, Anouar Benmalek, Olivier Trassard, Andoni Echaniz-Laguna, David Adams, Celine Labeyrie
Summary: This study aimed to assess the role of skin biopsy as a marker of disease onset and severity in hereditary transthyretin amyloidosis with polyneuropathy (ATTRv-PN). The results showed that skin amyloid deposits are a marker of ATTRv-PN disease onset, and decreased intraepidermal nerve fiber density (IENFD) is a marker of disease progression.
EUROPEAN JOURNAL OF NEUROLOGY
(2022)
Article
Medicine, General & Internal
Julian D. Gillmore, Ed Gane, Jorg Taubel, Justin Kao, Marianna Fontana, Michael L. Maitland, Jessica Seitzer, Daniel O'Connell, Kathryn R. Walsh, Kristy Wood, Jonathan Phillips, Yuanxin Xu, Adam Amaral, Adam P. Boyd, Jeffrey E. Cehelsky, Mark D. McKee, Andrew Schiermeier, Olivier Harari, Andrew Murphy, Christos A. Kyratsous, Brian Zambrowicz, Randy Soltys, David E. Gutstein, John Leonard, Laura Sepp-Lorenzino, David Lebwohl
Summary: The gene-editing therapeutic agent NTLA-2001 effectively reduced serum TTR protein concentrations in patients with ATTR amyloidosis, showing potential safety and pharmacodynamic effects in clinical studies.
NEW ENGLAND JOURNAL OF MEDICINE
(2021)
Review
Medicine, General & Internal
Valentina Velez-Santamaria, Velina Nedkova-Hristova, Moises Morales de la Prida, Carlos Casasnovas
Summary: The aim of this review is to discuss current treatments and investigational products and their impact on patients with hereditary transthyretin amyloidosis with polyneuropathy (ATTRv-PN), as well as provide recommendations for monitoring disease progression and treatment efficacy.
INTERNATIONAL JOURNAL OF GENERAL MEDICINE
(2022)
Article
Radiology, Nuclear Medicine & Medical Imaging
Jerome Hodel, Samir Benadjaoud, Mohamed Amine Benadjaoud, Jean-Pascal Lefaucheur, Violaine Plante-Bordeneuve
Summary: This study evaluated the ability of magnetic resonance neurography (MRN) to distinguish patients with hereditary transthyretin-related amyloidosis with polyneuropathy (ATTRv-PN) and assessed its prognostic value. The results showed that LSP root enlargement and increased intraneural signal were closely associated with clinical impairment in patients.
EUROPEAN RADIOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Tatsufumi Murakami, Takeshi Yokoyama, Mineyuki Mizuguchi, Shigenobu Tone, Shizuka Takaku, Kazunori Sango, Hirotake Nishimura, Kazuhiko Watabe, Yoshihide Sunada
Summary: In this study, features of FAP with E61K TTR substitution were characterized, showing low amyloidogenic properties in vitro and in vivo. Apoptotic cells were observed in the nerve of patients, and chromatin condensation was confirmed in Schwann cells by electron microscopy. These findings suggest that E61K TTR may not contribute significantly to amyloid fibril formation, but Schwann cell apoptosis could be related to neurodegeneration in FAP.
JOURNAL OF NEUROCHEMISTRY
(2021)
Article
Clinical Neurology
Thomas H. Brannagan, Teresa Coelho, Annabel K. Wang, Michael J. Polydefkis, Peter J. Dyck, John L. Berk, Brian Drachman, Peter Gorevic, Carol Whelan, Isabel Conceicao, Violaine Plante-Bordeneuve, Giampaolo Merlini, Laura Obici, Josep Maria Campistol Plana, Josep Gamez, Arnt Kristen, Anna Mazzeo, Luca Gentile, Arvind Narayana, Kemi Olugemo, Peter Aquino, Merrill D. Benson, Morie Gertz
Summary: Inotersen treatment for over 3 years slowed the progression of polyneuropathy associated with hATTR, with no new safety signals observed.
JOURNAL OF NEUROLOGY
(2022)
Review
Biochemistry & Molecular Biology
Maike F. Dohrn, Sandra Ihne, Ute Hegenbart, Jessica Medina, Stephan L. Zuchner, Teresa Coelho, Katrin Hahn
Summary: The liver-derived transport protein transthyretin (TTR) is responsible for systemic hereditary and wild-type amyloidosis. Approved therapies include TTR stabilization and knockdown. Factors influencing the disease include tetramer dissociation, genetic mutations, and external factors, while approved small molecule drugs and siRNA have shown effectiveness in reducing TTR levels and improving patients' quality of life.
JOURNAL OF NEUROCHEMISTRY
(2021)
Article
Multidisciplinary Sciences
Dayoung Kim, Jeeyoung Oh, Hong Ki Min, Hae-Rim Kim, Kyomin Choi
Summary: This cross-sectional study retrospectively analyzed the outcomes of nailfold capillaroscopy (NFC) and clinical characteristics in patients and asymptomatic carriers with transthyretin (TTR) gene mutation. The study found that all participants showed microvascular abnormalities in NFC, highlighting the importance of early identification of carriers who may progress to symptomatic patients.
SCIENTIFIC REPORTS
(2022)
Article
Clinical Neurology
Shin-Joe Yeh, Ti-Yen Yeh, Yi-Shiang Wang, Chi-Chao Chao, Shiou-Ru Tzeng, Tsz-Yi Tang, Jung-Hsien Hsieh, Yu-Yu Kan, Wei-Kang Yang, Sung-Tsang Hsieh
Summary: Microangiopathy with thromboinflammation is characteristic of advanced-stage ATTRv nerves, which provides an add-on mechanism and therapeutic target for nerve degeneration.
ANNALS OF CLINICAL AND TRANSLATIONAL NEUROLOGY
(2023)
Article
Clinical Neurology
Ming-Chang Chiang, Ti-Yen Yeh, Jia-Ying Sung, Hsueh-Wen Hsueh, Yi-Hui Kao, Sung-Ju Hsueh, Kai-Chieh Chang, Fang-Ping Feng, Yea-Huey Lin, Chi-Chao Chao, Sung-Tsang Hsieh
Summary: This study found that in late-onset ATTRv-PN carriers, median conduction parameters were the most common neurophysiological abnormalities and served as surrogate signatures of small- and large-fiber impairment. The combination of median distal motor latency and IENF density can reflect early neuropathy in carriers.
EUROPEAN JOURNAL OF NEUROLOGY
(2021)
Article
Medicine, General & Internal
Maria do Carmo Vilas-Boas, Pedro Filipe Pereira Fonseca, Ines Martins Sousa, Marcio Neves Cardoso, Joao Paulo Silva Cunha, Teresa Coelho
Summary: This study aims to quantitatively characterize the gait pattern of patients with V30M ATTRv amyloidosis, providing information for better understanding, diagnosis, and disease progression evaluation. The results showed delayed toe-off, excessive pelvic rotation, hip extension and external transverse rotation, as well as knee flexion in patients, along with reduced ground reaction forces. These gait anomalies are not clinically quantified, and gait analysis may contribute to the assessment of disease progression, in addition to clinical evaluation.
JOURNAL OF CLINICAL MEDICINE
(2022)
Review
Clinical Neurology
Luisa Sousa, Teresa Coelho, Ricardo Taipa
Summary: Hereditary transthyretin amyloidosis primarily affects the peripheral nerves, heart, kidney, and eye, but recent studies have shown increasing involvement of the central nervous system. Symptoms of CNS dysfunction are becoming more apparent in patients with this condition, indicating that it may become a significant issue in patient management in the future.
Article
Clinical Neurology
Amir Dori, Michael Arad, Yishay Wasserstrum, Arthur Pollak, Vera Nikitin, Merav Ben-David, Jana Shamash, Ayelet Hashachar Nahum, Efrat Shavit-Stein, Liran Domachevsky, Rafael Kuperstein, Dan Dominissini, Natalia Shelestovich, Menachem Sadeh, Elon Pras, Lior Greenbaum
Summary: This study investigates the early symptoms and diagnostic features of amyloidosis caused by the transthyretin Ser77Tyr mutation in individuals of Jewish Yemenite descent in Israel. The results show that the probability of disease diagnosis increases with age, with initial symptoms commonly being sensory changes in the extremities, and erectile dysfunction being a common symptom in males. Electrophysiological studies reveal neuropathy and skin denervation, and cardiomyopathy is frequently identified. Symptoms may be absent in patients and common in amyloid-negative carriers.
ANNALS OF CLINICAL AND TRANSLATIONAL NEUROLOGY
(2023)
Article
Cardiac & Cardiovascular Systems
Ulrika Thelander, Gunilla T. Westermark, Gunnar Antoni, Sergio Estrada, Alice Zancanaro, Elisabet Ihse, Per Westermark
Summary: This study found that the binding of skeletal probes to amyloid-containing hearts is due to the presence of tiny calcification clusters, which are not directly associated with amyloid fibrils. Therefore, bone scans can be considered surrogate markers of ATTR amyloid, but caution is needed when estimating amyloid load or disease progression.
INTERNATIONAL JOURNAL OF CARDIOLOGY
(2022)
Letter
Biochemistry & Molecular Biology
Shojiro Ichimata, Nagaaki Katoh, Ryuta Abe, Tsuneaki Yoshinaga, Fuyuki Kametani, Masahide Yazaki, Yukiko Kusama, Kenji Sano, Takeshi Uehara, Yoshiki Sekijima
AMYLOID-JOURNAL OF PROTEIN FOLDING DISORDERS
(2022)
Letter
Biochemistry & Molecular Biology
Shojiro Ichimata, Yukiko Hata, Nagaaki Katoh, Fuyuki Kametani, Masahide Yazaki, Yoshiki Sekijima, Naoki Nishida
AMYLOID-JOURNAL OF PROTEIN FOLDING DISORDERS
(2022)
Article
Multidisciplinary Sciences
Diana Arseni, Masato Hasegawa, Alexey G. Murzin, Fuyuki Kametani, Makoto Arai, Mari Yoshida, Benjamin Ryskeldi-Falcon
Summary: Abnormal aggregation of TDP-43 is a defining pathological hallmark in ALS and FTLD, as well as in other diseases. Cryo-electron microscopy revealed an amyloid-like filament structure comprising a single protofilament with a unique double-spiral-shaped fold in aggregated TDP-43, different from in vitro-formed filaments. The presence of glycine and neutral polar residues facilitates numerous turns and restricts beta-strand length, resulting in an absence of beta-sheet stacking and unique ligand-binding site possibilities. These findings enhance our understanding of ALS and FTLD molecular pathogenesis and inform the development of diagnostic and therapeutic agents targeting aggregated TDP-43.
Article
Pathology
Shinya Miyazaki, Yuki Kobayashi, Fuyuki Kametani, Kyoko Kobayashi, Susumu Iwaide, Tokuma Yanai, Tomoaki Murakami
Summary: This study reported a case of EFEMP1-derived amyloidosis in a 15-year-old Tsushima leopard cat, which is the first case found in animals. The characteristics of this case were different from human EFEMP1-derived amyloidosis, including the sites of amyloid deposition and the amyloidogenic region of the EFEMP1 protein.
VETERINARY PATHOLOGY
(2022)
Review
Biochemistry & Molecular Biology
Wataru Araki, Fuyuki Kametani
Summary: Soluble oligomeric assemblies of amyloid beta-protein (A beta), called A beta oligomers (A beta Os), play a critical role in the pathological progression of Alzheimer's disease (AD). Recent studies have shown that small molecules with antioxidative properties can reduce the neurotoxicity of A beta Os and have potential as drug candidates for the prevention and treatment of AD.
Letter
Biochemistry & Molecular Biology
Keiji Hirai, Shigeki Imamura, Aizan Hirai, Naoka Umemoto, Hisashi Oshiro, Fuyuki Kametani, Nagaaki Katoh, Masahide Yazaki, Susumu Ookawara, Yoshiyuki Morishita
AMYLOID-JOURNAL OF PROTEIN FOLDING DISORDERS
(2022)
Letter
Biochemistry & Molecular Biology
Nobuhiko Ohashi, Nagaaki Katoh, Kazuki Kasuga, Tsuneaki Yoshinaga, Fuyuki Kametani, Masahide Yazaki, Yoshiki Sekijima
AMYLOID-JOURNAL OF PROTEIN FOLDING DISORDERS
(2022)
Article
Pathology
Kyoko Kobayashi, Susumu Iwaide, Hiroki Sakai, Fuyuki Kametani, Tomoaki Murakami
Summary: This study identified the presence of cutaneous keratinic amyloid deposition in dogs and identified CK5 as an amyloid precursor protein. There was a significantly higher incidence of amyloid deposition in Shiba dogs, and CK5 amino acid polymorphisms were identified in these dogs.
VETERINARY PATHOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Hiroki Miyahara, Jian Dai, Ying Li, Xiaoran Cui, Hibiki Takeuchi, Naomi Hachiya, Fuyuki Kametani, Masahide Yazaki, Masayuki Mori, Keiichi Higuchi
Summary: This study investigates the role of reticuloendothelial macrophages in amyloid degradation and disease progression. Results show that these macrophages efficiently engulf and remove deposited amyloid, highlighting their importance in the early stages of amyloidosis. Maintaining phagocytic integrity may be a therapeutic strategy to inhibit disease progression.
AMYLOID-JOURNAL OF PROTEIN FOLDING DISORDERS
(2023)
Article
Medicine, General & Internal
Kazuna Ikeda, Daisuke Yamamoto, Keiko Usui, Hiroki Takeuchi, Nobuyuki Oka, Nagaaki Katoh, Masahide Yazaki, Fuyuki Kametani, Ichizo Nishino, Shin Hisahara
Summary: We present a case of a 68-year-old Japanese man with sporadic variant transthyretin (ATTRv) amyloidosis, carrying the novel variant A97D (p.A117D) in TTR. He exhibited slow progression of asymmetric neuropathy, unintentional weight loss, mild autonomic failure, and mild cardiomyopathy. Gastric duodenal mucosa showed deposition of TTR amyloid. In silico analyses predicted that TTR A97D (p.A117D) alters protein structure and function. ATTRv amyloidosis is challenging to diagnose in non-endemic regions due to its diverse phenotypes, including atypical peripheral nerve involvement and rare family history.
Article
Pathology
Tomoaki Murakami, Toshisuke Kaku, Kaori Tsukakoshi, Susumu Iwaide, Yoshiyuki Itoh, Miki Hisada, Kohji Nomura, Rikako Kubo, Kazunori Ikebukuro, Yukiko Sassa-O'Brien, Fuyuki Kametani
Summary: This study identified a novel amyloid precursor protein, alpha-S1-casein (CASA1), in canine mammary tumor-associated amyloidosis (MTAA) and elucidated its etiology. The truncation of CASA1's N-terminal region and its excessive synthesis were found to be responsible for the amyloid formation in MTAA. These findings provide valuable insights into the understanding of related proteopathies.
VETERINARY PATHOLOGY
(2023)
Article
Pathology
Ying Li, Jian Dai, Fuyuki Kametani, Masahide Yazaki, Akihito Ishigami, Masayuki Mori, Hiroki Miyahara, Keiichi Higuchi
Summary: Spontaneous and age-related amyloidosis were observed in C57BL/6J mice, characterized by the deposition of amyloid in the glomeruli. The amyloid fibril protein was identified as wild-type ApoA-II. Induction of amyloid deposition in younger mice resulted in kidney damage, indicating the pathological effects of amyloid deposition on renal function.
AMERICAN JOURNAL OF PATHOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Yoshinori Tanaka, Shun-ichi Ito, Yuki Honma, Masato Hasegawa, Fuyuki Kametani, Genjiro Suzuki, Lina Kozuma, Kosuke Takeya, Masumi Eto
Summary: The secretion of TDP-43 is stimulated by the inhibition of the autophagy-lysosomal pathway driven by the protein progranulin (PGRN). This dysregulation promotes the cell-to-cell spread of TDP-43 and may contribute to the progression of amyotrophic lateral sclerosis and frontotemporal lobar degeneration.
JOURNAL OF BIOLOGICAL CHEMISTRY
(2023)
Article
Multidisciplinary Sciences
Diana Arseni, Renren Chen, Alexey G. Murzin, Sew Y. Peak-Chew, Holly J. Garringer, Kathy L. Newell, Fuyuki Kametani, Andrew C. Robinson, Ruben Vidal, Bernardino Ghetti, Masato Hasegawa, Benjamin Ryskeldi-Falcon
Summary: The abnormal assembly of TDP-43 is associated with ALS and FTLD. Different brain distributions of assembled TDP-43 are observed in different types of FTLD-TDP. This study reveals the structure of assembled TDP-43 in type A FTLD-TDP and identifies new post-translational modifications, which may contribute to filament formation and structural variation.
Article
Urology & Nephrology
Yuki Shimamoto, Naoki Takahashi, Nagaaki Katoh, Yuki Matsui, Yusuke Mochizuki, Masanori Ito, Masahide Yazaki, Fuyuki Kametani, Kenji Kasuno, Yoshiki Sekijima, Hironobu Naiki, Masayuki Iwano
Summary: A case of light and heavy chain deposition disease (LHCDD) with focal amyloid deposition was diagnosed in a 79-year-old Japanese woman with nephrotic syndrome. The glomerular deposits were mainly composed of light chain as confirmed by mass spectrometry. This is the first reported case of LHCDD with focal amyloid deposition diagnosed by analysing the deposits with mass spectrometry.