研究者詳細 - 手塚　俊樹

論文 - 手塚　俊樹

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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年09月

ISSN 0969-9961

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.

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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年07月

ISSN 0918-2918

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.

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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年05月

ISSN 0918-2918

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.

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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年04月

ISSN 2045-2322

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.

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【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年04月

ISSN 0016-5980

Validation study of the Japanese version of the King's Parkinson's Disease Pain Scale and the King's Parkinson's Disease Pain Questionnaire

Kurihara, K., Fujioka, S., Mizutani, Y., Watanabe, H., Iwaoka, K., Maeda, T., Seki, M., Tezuka, T., Nakahara, J., Konno, T., Ishiguro, T., Onodera, O., Asano, Y., Takahashi, K., Rizos, A., Chaudhuri, K. R. and Tsuboi, Y.

Parkinsonism Relat Disord 120 106012 2024年03月

ISSN 1353-8020

INTRODUCTION: The King's Parkinson's Disease Pain Scale (KPPS)/King's Parkinson's Disease Pain Questionnaire (KPPQ) was developed as a tool to quantitatively assess pain in patients with Parkinson's disease (PwPD). Here, we conducted a Japanese multicenter validation study to verify the reliability of KPPS/KPPQ in Japanese PwPD. METHODS: PwPD, ≥20 years, with unexplained pain were included; those with a definitive primary cause of pain other than PD were excluded. A total of 151 patients who fulfilled the criteria were analyzed, and test-retest reliability was investigated in 25 individuals. RESULTS: The 151 patients included 101 women (66.9 %); mean age 68.3 ± 9.9 years, mean disease duration 9.2 ± 5.2 years. The most frequent pain type in the KPPS classification was musculoskeletal pain (82.8 %). There was a positive correlation between KPPS total score and the Non-Motor Symptoms Scale (NMSS) total score, NMSS item 27, the Parkinson's disease sleep scale-version 2 (PDSS-2) total score, PDSS-2 item 10, the Parkinson's Disease Questionnaire-8 (PDQ-8) summary index and PDQ-8 item 7. Cronbach's alpha of KPPS was 0.626 (0.562-0.658) and the intraclass correlation coefficient of test-retest reliability was 0.740. Cronbach's alpha of KPPQ was 0.660 (0.617-0.705) and a test-retest reliability of kappa coefficient was 0.593 (0.0-1.0). CONCLUSIONS: KPPS correlated well with other scales for assessing pain. KPPS correlated well with patients' quality of life, non-motor symptoms, and sleep disturbances. The reproducibility of KPPS/KPPQ makes it suitable for continuous evaluation of the same patient. On the other hand, the internal consistency of KPPS/KPPQ is rather low.

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パーキンソン病に対する脳深部刺激療法後に4-condition testが病態の把握に有用であった1例

大草, 翔平, 大河内, 遼太郎, 坂井, 悠人, 忽滑谷, 智紀, 小杉, 健三, 工藤, 駿, 手塚, 俊樹, 二瓶, 義廣, 秋山, 武紀, 内田, 裕之, 三村, 將, 戸田, 正博, 小林, 正人, 中原, 仁 and 関, 守信

日本定位・機能神経外科学会プログラム・抄録集 63回 121 2024年01月

Systemic lupus erythematosus mimicking retinal migraine: a case report

Tezuka, T., Shibata, M., Hanaoka, H., Izawa, Y., Kikuchi, T., Akino, K., Ozawa, Y., Saito, M., Kaneko, Y., Nakahara, J. and Takizawa, T.

Cephalalgia 43 （ 12 ） 3331024231219477 2023年12月

ISSN 0333-1024

BACKGROUND: Retinal migraine is a diagnosis of exclusion and is characterized by repeated episodes of transient monocular blindness associated with migraine. We report a case of systemic lupus erythematosus with acute episodes mimicking retinal migraines. CASE REPORT: A 46-year-old woman with a history of migraine with aura since her 20s and Evans syndrome presented with episodic transient monocular blindness. Retinal migraine was considered as the cause, and migraine prophylaxis initially reduced its frequency. After 5 months, the frequency increased, with chilblain-like lupus lesions on her extremities. Laboratory testing revealed lymphopenia and hypocomplementemia, fulfilling the diagnostic criteria for systemic lupus erythematosus, which may have caused Evans syndrome and transient monocular blindness, mimicking retinal migraines. After intravenous methylprednisolone and rituximab therapy, the transient monocular blindness episodes did not recur. CONCLUSION: Given the clinical presentation, systemic lupus erythematosus should be considered as a cause of transient monocular blindness and should be distinguished from retinal migraine.

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【腫瘍随伴症候群】免疫学的機序によるもの　抗NMDA受容体抗体脳炎

手塚, 俊樹 and 鈴木, 重明

臨床検査 67 （ 11 ） 1278 - 1283 2023年11月

ISSN 0485-1420

＜文献概要＞POINT　●抗N-メチル-D-アスパラギン酸(NMDA)受容体抗体脳炎は,最も頻度が高い自己免疫性脳炎であり,急性・亜急性に発症する精神症状を特徴とし,抗NMDA受容体抗体によるNMDA受容体の内在化と機能低下が主な病態である.●抗NMDA受容体抗体の測定法としては,CBA法と免疫組織化学染色(IHC)を用いたTBA法があり,いずれの方法も血清・髄液における抗NMDA受容体抗体の検出が可能であるが,髄液のほうが感度・特異度ともに優れている.●わが国における抗NMDA抗体の測定法に関しては,商業ベースのCBA法があるが,保険適用外の検査であり,結果が出るまでに週単位の時間がかかる.より精度の高いTBA法に関しては,さらに施行可能な施設が限られる.●抗NMDA受容体抗体が治療により減少することで,内在化したNMDA受容体が再度シナプス膜上に戻り回復するため,早期の診断と免疫治療が患者の生命,機能予後の改善に重要である.

脊髄血管造影が鑑別の一助となった脊髄High-grade gliomaの一例

吉田, 昌平, 徳安, 大輝, 高橋, 洵行, 関口, 耕史, 手塚, 俊樹, 勝又, 雅裕, 伊澤, 良兼 and 中原, 仁

臨床神経学 63 （ 11 ） 768 2023年11月

ISSN 0009-918X

Source-based morphometryを用いた機械学習モデルでの神経認知障害のアミロイドβ予測

百田, 友紀, 文, 鐘玉, 平野, 仁一, 神谷, 慶, 上田, 亮, 岩渕, 雄, 高畑, 圭輔, 山本, 保天, 手塚, 俊樹, 窪田, 真人, 関, 守信, 色本, 涼, 三村, 悠, 岸本, 泰士郎, 田渕, 肇, 陣崎, 雅弘, 伊東, 大介 and 三村, 將

Dementia Japan 37 （ 4 ） 657 2023年10月

ISSN 1342-646X

Performance of plasma Aβ42/40, measured using a fully automated immunoassay, across a broad patient population in identifying amyloid status

Bun, S., Ito, D., Tezuka, T., Kubota, M., Ueda, R., Takahata, K., Moriguchi, S., Kurose, S., Momota, Y., Suzuki, N., Morimoto, A., Hoshino, Y., Seki, M., Mimura, Y., Shikimoto, R., Yamamoto, Y., Hoshino, T., Sato, Y., Tabuchi, H. and Mimura, M.

Alzheimers Res Ther 15 （ 1 ） 149 2023年09月

BACKGROUND: Plasma biomarkers have emerged as promising screening tools for Alzheimer's disease (AD) because of their potential to detect amyloid β (Aβ) accumulation in the brain. One such candidate is the plasma Aβ42/40 ratio (Aβ42/40). Unlike previous research that used traditional immunoassay, recent studies that measured plasma Aβ42/40 using fully automated platforms reported promising results. However, its utility should be confirmed using a broader patient population, focusing on the potential for early detection. METHODS: We recruited 174 participants, including healthy controls (HC) and patients with clinical diagnoses of AD, frontotemporal lobar degeneration, dementia with Lewy bodies/Parkinson's disease, mild cognitive impairment (MCI), and others, from a university memory clinic. We examined the performance of plasma Aβ42/40, measured using the fully automated high-sensitivity chemiluminescence enzyme (HISCL) immunoassay, in detecting amyloid-positron emission tomography (PET)-derived Aβ pathology. We also compared its performance with that of Simoa-based plasma phosphorylated tau at residue 181 (p-tau181), glial fibrillary acidic protein (GFAP), and neurofilament light (NfL). RESULTS: Using the best cut-off derived from the Youden Index, plasma Aβ42/40 yielded an area under the receiver operating characteristic curve (AUC) of 0.949 in distinguishing visually assessed (18)F-Florbetaben amyloid PET positivity. The plasma Aβ42/40 had a significantly superior AUC than p-tau181, GFAP, and NfL in the 167 participants with measurements for all four biomarkers. Next, we analyzed 99 participants, including only the HC and those with MCI, and discovered that plasma Aβ42/40 outperformed the other plasma biomarkers, suggesting its ability to detect early amyloid accumulation. Using the Centiloid scale (CL), Spearman's rank correlation coefficient between plasma Aβ42/40 and CL was -0.767. Among the 15 participants falling within the CL values indicative of potential future amyloid accumulation (CL between 13.5 and 35.7), plasma Aβ42/40 categorized 61.5% (8/13) as Aβ-positive, whereas visual assessment of amyloid PET identified 20% (3/15) as positive. CONCLUSION: Plasma Aβ42/40 measured using the fully automated HISCL platform showed excellent performance in identifying Aβ accumulation in the brain in a well-characterized cohort. This equipment may be useful for screening amyloid pathology because it has the potential to detect early amyloid pathology and is readily applied in clinical settings.

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"Missing-piece" sign with dural arteriovenous fistula at craniocervical junction: A case report

Tezuka, T., Nukariya, T., Katsumata, M., Miyauchi, T., Tokuyasu, D., Azami, S., Izawa, Y., Nagoshi, N., Fujiwara, H., Mizutani, K., Akiyama, T., Toda, M., Nakahara, J. and Nishimoto, Y.

J Stroke Cerebrovasc Dis 32 （ 7 ） 107152 2023年07月

ISSN 1052-3057

OBJECTIVES: Spinal dural arteriovenous fistula (sDAVF) is a rare and often underdiagnosed spinal disease. Early diagnosis is required because the deficits are reversible and delays in treatment cause permanent morbidity. Although the abnormal vascular flow void is a critical radiographic feature of sDAVF, they are not always present. A characteristic enhancement pattern of sDAVF has been recently reported as the "missing-piece" sign which can lead to the early and correct diagnosis. METHODS: We presented imaging findings, treatment decisions, and the outcome of a rare case of sDAVF, in which the "missing-piece" sign appeared atypical. RESULTS: A 60-year-old woman developed numbness and weakness in her extremities. Spinal MRI revealed longitudinal hyperintensity in the T2-weighted image, extending from the thoracic level to medulla oblongata. At first, myelopathy with inflammation or tumor was suspected because of the lack of flow voids and vascular abnormalities in CT-angiography and MR-DSA. However, we administered intravenous methylprednisolone and her symptom got worse with the appearance of the "missing-piece" sign. Then, we successfully diagnosed sDAVF by angiography. The "missing-piece" sign was considered to derive from inconsistency of the intrinsic venous system of spinal cord, with the abrupt segments without enhancement. The same etiology was considered in our case. CONCLUSIONS: Detecting the "missing-piece" sign can lead to the correct diagnosis of sDAVF, even if the sign appeared atypical.

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Dysautonomia associated with immune checkpoint inhibitors

Tezuka, T., Okuzumi, S., Nakashima, C., Ide, T., Imai, S., Mitsuboshi, S., Kuwahara, Y., Takizawa, T., Seki, M., Minematsu, N., Aragane, N., Nakahara, J., Hori, S., Nakane, S. and Suzuki, S.

J Neurol 270 （ 7 ） 3413 - 3423 2023年07月

ISSN 0340-5354

OBJECTIVE: The purpose of this study is to report the clinical characteristics of dysautonomia associated with immune checkpoint inhibitors (ICIs). METHODS: We reported two patients with autoimmune autonomic ganglionopathy (AAG) occurring as immune-related adverse events (irAEs). We also performed a review of previous case reports presenting dysautonomia during ICI therapy. Moreover, we conducted pharmacovigilance analyses using the US Food and Drug Administration Adverse Events Reporting System (FAERS) to investigate dysautonomia associated with ICI. RESULTS: Two patients in our care developed both AAG and autoimmune encephalitis following ICI therapy for lung cancers. We comprehensively reviewed 13 published cases (M:F = 11:2, mean onset age of 53 years) with ICI-associated dysautonomia including AAG (n = 3) and autonomic neuropathy (n = 10). Of these, ICI monotherapy was performed in seven and combination ICI use in six. In 6 of 13 patients, dysautonomia appeared within one month after the start of ICIs. Orthostatic hypotension was observed in 7 and urinary incontinence or retention in five. All patients except three showed gastrointestinal symptoms. Anti-ganglionic acetylcholine receptor antibodies were undetectable. All but two patients received immune-modulating therapy. Immuno-modulating therapy was effective in three patients with AAG and two patients with autonomic neuropathy, but ineffective in the others. Five patients died, of either the neurological irAE (n = 3) or cancer (n = 2). The pharmacovigilance analyses using FAERS showed that ipilimumab monotherapy and the combination of nivolumab and ipilimumab constituted significant risks for developing dysautonomia, consistent with the review of literature. CONCLUSION: ICIs can cause dysautonomia including AAG, and autonomic neuropathy is a neurological irAE.

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パーキンソン病患者に対するオンラインリハビリの日常生活動作と生活の質への影響

大草, 翔平, 三枝, 洋喜, 宮川, 和也, 堤, 裕太, 石田, 沙瑛, 西潟, 京子, 忽滑谷, 智紀, 手塚, 俊樹, 二瓶, 義廣, 北川, 泰啓, 久保, 紳一郎, 鈴木, 則宏, 中原, 仁 and 関, 守信

パーキンソン病・運動障害疾患コングレスプログラム・抄録集 17回 102 2023年07月

Anti-N-methyl-D-aspartate receptor encephalitis with concurrent human herpes virus-6A deoxyribonucleic acid detection: An autopsy case

Shimohama, S., Iizuka, T., Takizawa, T., Watanabe, N., Tezuka, T., Matsuda, K., Yamanoi, K., Kanazawa, N., Kawamura, Y., Yoshikawa, T., Suzuki, T., Takao, M., Nakahara, J. and Izawa, Y.

Neuropathology 43 （ 3 ） 257 - 261 2023年06月

ISSN 0919-6544

We report an autopsy case of anti-N-methyl-D-aspartate (NMDA) receptor (NMDAR) encephalitis with concurrent human herpes virus-6 (HHV-6) A deoxyribonucleic acid (DNA) detection in cerebrospinal fluid (CSF). A 38-year-old previously healthy Japanese man presented with a generalized seizure. Brain magnetic resonance imaging (MRI) findings were unremarkable, but CSF revealed pleocytosis. On Day 11, HHV-6 DNA was detected in CSF, and IgG antibodies against the NR1 subunit of the NMDAR (GluN1) were subsequently detected. Since HHV-6 encephalitis was initially suspected, the patient was treated with foscarnet and ganciclovir, but the HHV-6A copy number increased from 200 (Day 22) to 2000 copies/mL (Day 47), and the therapy was ineffective. As typical symptoms of anti-NMDAR encephalitis developed, we changed the patient's treatment to combat anti-NMDAR encephalitis. He was repeatedly treated with first-line immunotherapy, and GluN1 antibody titer decreased. He was not treated with second-line immunotherapy because of recurrent infections; he died on Day 310. Postmortem examinations did not show systemic tumors. Microscopic examination of the brain revealed only severe neuronal rarefaction in the hippocampal cornu ammonis (CA) 3-4 areas with gliosis. Early initiation of aggressive immunotherapy may be required in a refractory case of anti-NMDAR encephalitis, even with HHV-6A DNA detection, because the significance of this concurrent detection in autoimmune encephalitis remains unclear.

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ニボルマブ投与後に心筋炎を合併したirAE筋炎の1例

忽滑谷, 智紀, 徳安, 大輝, 手塚, 俊樹, 西本, 祥仁, 水野, 里香, 浜本, 康夫, 鈴木, 重明 and 中原, 仁

日本内科学会関東地方会 685回 41 2023年03月

免疫チェックポイント阻害剤関連の自律神経障害

手塚, 俊樹, 奥隅, 真一, 中島, 千穂, 今井, 俊吾, 峰松, 直人, 荒金, 尚子, 滝沢, 翼, 関, 守信, 中原, 仁 and 鈴木, 重明

日本内科学会雑誌 112 （臨増） 188 2023年02月

ISSN 0021-5384

Impact of Amyloid and Tau PET on Changes in Diagnosis and Patient Management

Shimohama, S., Tezuka, T., Takahata, K., Bun, S., Tabuchi, H., Seki, M., Momota, Y., Suzuki, N., Morimoto, A., Iwabuchi, Y., Kubota, M., Yamamoto, Y., Sano, Y., Shikimoto, R., Funaki, K., Mimura, Y., Nishimoto, Y., Ueda, R., Jinzaki, M., Nakahara, J., Mimura, M. and Ito, D.

Neurology 100 （ 3 ） e264 - e274 2023年01月

ISSN 0028-3878

BACKGROUND AND OBJECTIVES: Previous studies have evaluated the diagnostic effect of amyloid PET in selected research cohorts. However, these studies did not assess the clinical impact of the combination of amyloid and tau PETs. Our objective was to evaluate the association of the combination of 2 PETs with changes in diagnosis, treatment, and management in a memory clinic cohort. METHODS: All participants underwent amyloid [(18)F]florbetaben PET and tau PET using [(18)F]PI-2620 or [(18)F]Florzolotau, which are potentially useful for the diagnosis of non-Alzheimer disease (AD) tauopathies. Dementia specialists determined a pre- and post-PET diagnosis that existed in both a clinical syndrome (cognitive normal [CN], mild cognitive impairment [MCI], and dementia) and suspected etiology, with a confidence level. In addition, the dementia specialists determined patient treatment in terms of ancillary investigations and management. RESULTS: Among 126 registered participants, 84.9% completed the study procedures and were included in the analysis (CN [n = 40], MCI [n = 25], AD [n = 20], and non-AD dementia [n = 22]). The etiologic diagnosis changed in 25.0% in the CN, 68.0% in the MCI, and 23.8% with dementia. Overall changes in management between pre- and post-PET occurred in 5.0% of CN, 52.0% of MCI, and 38.1% of dementia. Logistic regression analysis revealed that tau PET has stronger associations with change management than amyloid PET in all participants and dementia groups. DISCUSSION: The combination of amyloid and tau PETs was associated with changes in management and diagnosis of MCI and dementia, and the second-generation tau PET has a strong impact on the changes in diagnosis and management in memory clinics. CLASSIFICATION OF EVIDENCE: This study provides Class I evidence that the combination of amyloid and tau PETs was associated with changes in management and diagnosis of MCI and dementia.

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Findings of (18) F-PI-2620 tau PET imaging in patients with Alzheimer's disease and healthy controls in relation to the plasma P-tau181 levels in a Japanese sample

Bun, S., Moriguchi, S., Tezuka, T., Sato, Y., Takahata, K., Seki, M., Nakajima, S., Yamamoto, Y., Sano, Y., Suzuki, N., Morimoto, A., Ueda, R., Tabuchi, H., Ito, D. and Mimura, M.

Neuropsychopharmacol Rep 42 （ 4 ） 437 - 448 2022年12月

ISSN 2574-173x

BACKGROUND: Alzheimer's disease (AD) is the most common cause of dementia worldwide. In AD, abnormal tau accumulates within neurons of the brain, facilitated by extracellular β-amyloid deposition, leading to neurodegeneration, and eventually, cognitive impairment. As this process is thought to be irreversible, early identification of abnormal tau in the brain is crucial for the development of new therapeutic interventions. AIMS: (18) F-PI-2620 is one of the second-generation tau PET tracers with presumably less off-target binding than its predecessors. Although a few clinical studies have recently reported the use of (18) F-PI-2620 tau PET in patients with AD, its applicability to AD is yet to be thoroughly examined. METHODS: In the present pilot study, we performed (18) F-PI-2620 tau PET in seven cases of probable AD (AD group) and seven healthy controls (HC group). Standardized uptake value ratios (SUVR) in regions of interest (ROIs) in the medial temporal region and neocortex were compared between the AD and HC groups. Furthermore, correlations between regional SUVR and plasma p-tau181 as well as cognitive test scores were also analyzed. RESULTS: The uptake of (18) F-PI-2620 was distinctly increased in the AD group across all the ROIs. SUVR in all the target ROIs were significantly correlated with plasma p-tau181 levels, as well as with MMSE and ADAS-cog scores. DISCUSSION & CONCLUSION: Our results add to accumulating evidence suggesting that (18) F-PI-2620 is a promising tau PET tracer that allows patients with AD to be distinguished from healthy controls, although a study with a larger sample size is warranted.

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