Tezuka, Toshiki

写真a

Affiliation

School of Medicine, Department of Internal Medicine (Neurology) (Shinanomachi)

Position

Senior Assistant Professor (Non-tenured)/Assistant Professor (Non-tenured)

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Papers 【 Display / hide 】

  • Clinical characteristics and pathophysiological properties of newly discovered LRRK2 variants associated with Parkinson's disease

    Tezuka, T., Ishiguro, M., Taniguchi, D., Osogaguchi, E., Shiba-Fukushima, K., Ogata, J., Ishii, R., Ikeda, A., Li, Y., Yoshino, H., Matsui, T., Kaida, K., Funayama, M., Nishioka, K., Kumazawa, F., Matsubara, T., Tsuda, H., Saito, Y., Murayama, S., Imai, Y. and Hattori, N.

    Neurobiol Dis 199   106571 2024.09

    ISSN  0969-9961

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    Leucine-rich repeat kinase 2 (LRRK2) is the most common gene responsible for familial Parkinson's disease (PD). The gene product of LRRK2 contains multiple protein domains, including armadillo repeat, ankyrin repeat, leucine-rich repeat (LRR), Ras-of-complex (ROC), C-terminal of ROC (COR), kinase, and WD40 domains. In this study, we performed genetic screening of LRRK2 in our PD cohort, detecting sixteen LRRK2 rare variants. Among them, we selected seven variants that are likely to be familial and characterized them in terms of LRRK2 protein function, along with clinical information and one pathological analysis. The seven variants were S1120P and N1221K in the LRR domain; I1339M, S1403R, and V1447M in the ROC domain; and I1658F and D1873H in the COR domain. The kinase activity of the LRRK2 variants N1221K, S1403R, V1447M, and I1658F toward Rab10, a well-known phosphorylation substrate, was higher than that of wild-type LRRK2. LRRK2 D1873H showed enhanced self-association activity, whereas LRRK2 S1403R and D1873H showed reduced microtubule-binding activity. Pathological analysis of a patient with the LRRK2 V1447M variant was also performed, which revealed Lewy pathology in the brainstem. No functional alterations in terms of kinase activity, self-association activity, and microtubule-binding activity were detected in LRRK2 S1120P and I1339M variants. However, the patient with PD carrying LRRK2 S1120P variant also had a heterozygous Glucosylceramidase beta 1 (GBA1) L444P variant. In conclusion, we characterized seven LRRK2 variants potentially associated with PD. Five of the seven variants in different LRRK2 domains exhibited altered properties in kinase activity, self-association, and microtubule-binding activity, suggesting that each domain variant may contribute to disease progression in different ways.

  • Repeated Intravenous Methylprednisolone May Prevent Deterioration of Hypertrophic Pachymeningitis in Rosai-Dorfman Disease

    Tezuka, T., Nukariya, T., Takahashi, N., Kufukihara, K., Tsuyama, N., Terui, Y., Kameyama, K., Nakahara, J. and Takizawa, T.

    Intern Med  2024.07

    ISSN  0918-2918

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    Rosai-Dorfman disease (RDD) is a rare form of non-Langerhans cell histiocytosis. Although 20% of patients with RDD have spontaneous remission, some cases with central nervous system (CNS) involvement require surgery or systemic treatment. We encountered a case of RDD in which hypertrophic pachymeningitis was diffuse, eliminating the need for surgical intervention. A 72-year-old Japanese man was diagnosed with RDD based on pathological lymph node findings. Repeated intravenous methylprednisolone (IVMP) administration resolved and stabilized the hypertrophic pachymeningitis without any sequelae. If surgery or anticancer medications are contraindicated, repeated IVMP may be a good therapeutic option for CNS-associated RDD.

  • Cerebral Venous Thrombosis Mimicking Limbic Encephalitis

    Tezuka, T., Takahashi, N., Tokuyasu, D., Azami, S., Sekiguchi, K., Takizawa, T., Izawa, Y., Nakahara, J. and Katsumata, M.

    Intern Med 63 ( 9 ) 1277 - 1280 2024.05

    ISSN  0918-2918

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    Cerebral venous thrombosis (CVT) is challenging to diagnose, as it presents with variable symptoms. We encountered a complicated case of CVT that mimicked limbic encephalitis due to sensory aphasia. Based on the characteristic magnetic resonance imaging findings, this 72-year-old Japanese man was later confirmed to have CVT, the cause of which was periodontitis due to Eikenella corrodens, a Gram-negative facultative anaerobic that is part of the mouth's normal flora. The symptoms improved without sequelae following anticoagulation treatment and antibiotics. Clinicians should consider CVT as a differential diagnosis when unexplainable neurological symptoms suggesting limbic encephalitis are observed.

  • Amyloid-β prediction machine learning model using source-based morphometry across neurocognitive disorders

    Momota, Y., Bun, S., Hirano, J., Kamiya, K., Ueda, R., Iwabuchi, Y., Takahata, K., Yamamoto, Y., Tezuka, T., Kubota, M., Seki, M., Shikimoto, R., Mimura, Y., Kishimoto, T., Tabuchi, H., Jinzaki, M., Ito, D. and Mimura, M.

    Sci Rep 14 ( 1 ) 7633 2024.04

    ISSN  2045-2322

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    Previous studies have developed and explored magnetic resonance imaging (MRI)-based machine learning models for predicting Alzheimer's disease (AD). However, limited research has focused on models incorporating diverse patient populations. This study aimed to build a clinically useful prediction model for amyloid-beta (Aβ) deposition using source-based morphometry, using a data-driven algorithm based on independent component analyses. Additionally, we assessed how the predictive accuracies varied with the feature combinations. Data from 118 participants clinically diagnosed with various conditions such as AD, mild cognitive impairment, frontotemporal lobar degeneration, corticobasal syndrome, progressive supranuclear palsy, and psychiatric disorders, as well as healthy controls were used for the development of the model. We used structural MR images, cognitive test results, and apolipoprotein E status for feature selection. Three-dimensional T1-weighted images were preprocessed into voxel-based gray matter images and then subjected to source-based morphometry. We used a support vector machine as a classifier. We applied SHapley Additive exPlanations, a game-theoretical approach, to ensure model accountability. The final model that was based on MR-images, cognitive test results, and apolipoprotein E status yielded 89.8% accuracy and a receiver operating characteristic curve of 0.888. The model based on MR-images alone showed 84.7% accuracy. Aβ-positivity was correctly detected in non-AD patients. One of the seven independent components derived from source-based morphometry was considered to represent an AD-related gray matter volume pattern and showed the strongest impact on the model output. Aβ-positivity across neurological and psychiatric disorders was predicted with moderate-to-high accuracy and was associated with a probable AD-related gray matter volume pattern. An MRI-based data-driven machine learning approach can be beneficial as a diagnostic aid.

  • 【10年間で登場した薬剤の市販後を総点検!病棟頻用薬の通信簿】(PART.2)承認後3年〜7年未満(2018〜2021)　新規MAO-B阻害薬　サフィナミド,ラサギリン

    手塚, 俊樹 and 関, 守信

    薬事 66 ( 6 ) 1135 - 1141 2024.04

    ISSN  0016-5980

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