Clinical neuropathological study on the associated neurological/psychiatric symptoms and the responsible lesion in argyria granule dementia

• Project/Area Number: 19K07988
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 52020:Neurology-related
• Research Institution: Tokyo Metropolitan Geriatric Hospital and Institute of Gerontology (2020-2022); National Center of Neurology and Psychiatry (2019)
• Principal Investigator: Saito Yuko 地方独立行政法人東京都健康長寿医療センター(東京都健康長寿医療センター研究所), 東京都健康長寿医療センター研究所, 研究部長 (60344066)
• Project Period (FY): 2019-04-01 – 2023-03-31
• Project Status: Completed (Fiscal Year 2022)
• Budget Amount: ¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000); Fiscal Year 2021: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000); Fiscal Year 2020: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2019: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
• Keywords: パーキンソニズム / タウオパチー / 高齢者 / 認知症 / 嗜銀顆粒 / 脳幹 / 線条体 / タウ / 黒質 / 精神症状 / 嗜顆粒性疾患 / 嗜銀顆粒性疾患 / うつ / 縫線核 / 気分障害 / 神経病理 / ステージング

Outline of Research at the Start

嗜銀顆粒性認知症は、本邦では認知症を来す比較的頻度の高い疾患である。我々は嗜銀顆粒性認知症のステージ分類を提唱し。ただし、「認知症」のステージとして、脳幹病変については含めていない。一方で、進行性核上性麻痺、レビー小体型認知症と誤診される例や内因性精神疾患の一部と診断された剖検例の中にも嗜銀顆粒性認知症の病理が見られる。そこで、本研究では、改めてその候補症例を抽出する試みを行うと共に、嗜銀顆粒性認知症の黒質・青斑核・縫線核を含む脳幹病変について検索を行い、脳幹病変の「現ステージ分類」での位置づけと臨床症状の相関を明らかにする。そして、それらの症状への早期介入方法や治療法の確立を目指す。

Outline of Final Research Achievements

Immunohistochemical investigation of the possibility that nigrostriatal dopaminergic neuron dysfunction in AGD may be the cause of parkinsonism (PA). AGD group with PA and dementia (DGP), AGD group with dementia and no PA (DG), normal control (NC) group, Parkinson's disease (PD) group, and PSP group. Immunostaining was performed. Evaluation using anti-tyrosine hydroxylase antibody and anti-dopamine transporter antibody. Brainstem cross-sections including the substantia nigra showed argyrophilic granules mainly in the substantia nigra in the DGP group, but not in the DG group. The striatum-positive fiber density was significantly decreased by DGD in the AGD group compared to NC. PA in AGD may be due to hypofunction of nigrostriatal dopaminergic neurons.

Academic Significance and Societal Importance of the Research Achievements

パーキンソニズムの原因として、嗜銀顆粒も関与することが明らかとなた。パーキンソニズムの病態を知るうえで、また、薬剤反応性の悪い群にこのような例が存在することが明らかとなった。

Research Products

• [Journal Article] Erdheim-Chester Disease Involving the Central Nervous System with Latent Toxoplasmosis (2022)
  • Author(s): Wadayama Tomoya、Shimizu Mikito、Kimura Ikko、Baba Kousuke、Beck Goichi、Nagano Seiichi、Morita Ryo、Nakagawa Hidenori、Shirano Michinori、Goto Tetsushi、Norose Kazumi、Hikosaka Kenji、Murayama Shigeo、Mochizuki Hideki
  • Journal Title: Internal Medicine Volume: 61 Issue: 17 Pages: 2661-2666
  • DOI: 10.2169/internalmedicine.8564-21
  • NAID: 130008158352
  • ISSN: 0918-2918, 1349-7235
  • Year and Date: 2022-09-01
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Pathology-associated change in levels and localization of SIDT2 in postmortem brains of Parkinson's disease and dementia with Lewy bodies patients (2022)
  • Author(s): Fujiwara Yuuki、Kabuta Chihana、Sano Terunori、Murayama Shigeo、Saito Yuko、Kabuta Tomohiro
  • Journal Title: Neurochemistry International Volume: 152 Pages: 105243-105243
  • DOI: 10.1016/j.neuint.2021.105243
  • Peer Reviewed
• [Journal Article] piRNA/PIWI Protein Complex as a Potential Biomarker in Sporadic Amyotrophic Lateral Sclerosis (2022)
  • Author(s): Abdelhamid Rehab F.、Ogawa Kotaro、Beck Goichi、Ikenaka Kensuke、Takeuchi Eriko、Yasumizu Yoshiaki、Jinno Jyunki、Kimura Yasuyoshi、Baba Kousuke、Nagai Yoshitaka、Okada Yukinori、Saito Yuko、Murayama Shigeo、Mochizuki Hideki、Nagano Seiichi
  • Journal Title: Molecular Neurobiology Volume: 59 Issue: 3 Pages: 1693-1705
  • DOI: 10.1007/s12035-021-02686-2
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Thymidine kinase 2 and mitochondrial protein COX I in the cerebellum of patients with spinocerebellar ataxia type 31 caused by penta-nucleotide repeats (TTCCA) n. (2022)
  • Author(s): Aoki H, Higashi M, Okita M, Ando N, Murayama S, Ishikawa K*, Yokota T.
  • Journal Title: Cerebellum. Volume: Jan 27 Issue: 1 Pages: 70-84
  • DOI: 10.1007/s12311-021-01364-2
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Hornerin deposits in neuronal intranuclear inclusion disease: direct identification of proteins with compositionally biased regions in inclusions (2022)
  • Author(s): Park Hongsun、Yamanaka Tomoyuki、Toyama Yumiko、Fujita Atsushi、Doi Hiroshi、Nirasawa Takashi、Murayama Shigeo、Matsumoto Naomichi、Shimogori Tomomi、Ikegawa Masaya、Haltia Matti J.、Nukina Nobuyuki
  • Journal Title: Acta Neuropathologica Communications Volume: 10 Issue: 1 Pages: 28-28
  • DOI: 10.1186/s40478-022-01333-8
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] 18F-THK5351 PET for visualizing predominant lesions of pathologically confirmed corticobasal degeneration presenting with frontal behavioral-spatial syndrome (2022)
  • Author(s): Saitoh Yuji、Imabayashi Etsuko、Mizutani Masashi、Tsukamoto Tadashi、Hasegawa Masato、Saito Yuko、Matsuda Hiroshi、Takahashi Yuji
  • Journal Title: Journal of Neurology Volume: 269 Issue: 9 Pages: 5157-5161
  • DOI: 10.1007/s00415-022-11121-y
  • Peer Reviewed / Open Access
• [Journal Article] Soluble APP-α and APP-β in cerebrospinal fluid as potential biomarkers for differential diagnosis of mild cognitive impairment (2022)
  • Author(s): Araki W, Kanemaru K, Hattori K, Tsukamoto T, Saito Y, Yoshida S, Takano H, Sakata M, Yokoi Y, Omachi Y, Nagaoka U, Nagao M, Komori T, Tachimori H, Murayama S, Mizusawa H.
  • Journal Title: Aging Clin Exp Res Volume: 34(2) Issue: 2 Pages: 341-347
  • DOI: 10.1007/s40520-021-01935-7
  • Peer Reviewed
• [Journal Article] Unique Lewy pathology in myotonic dystrophy type 1 (2022)
  • Author(s): Sano Terunori、Kawazoe Tomoya、Shioya Ayako、Mori‐Yoshimura Madoka、Oya Yasushi、Maruo Kazushi、Nishino Ichizo、Hoshino Mikio、Murayama Shigeo、Saito Yuko
  • Journal Title: Neuropathology Volume: - Issue: 2 Pages: 104-116
  • DOI: 10.1111/neup.12790
  • Peer Reviewed / Open Access
• [Journal Article] Autopsy Validation of the Diagnostic Accuracy of ¹²³I-Metaiodobenzylguanidine Myocardial Scintigraphy for Lewy Body Disease (2022)
  • Author(s): Matsubara Tomoyasu、Kameyama Masashi、Tanaka Noriko、Sengoku Renpei、Orita Makoto、Furuta Ko、Iwata Atsushi、Arai Tomio、Maruyama Hirofumi、Saito Yuko、Murayama Shigeo
  • Journal Title: Neurology Volume: 98 Issue: 16
  • DOI: 10.1212/wnl.0000000000200110
  • Peer Reviewed / Open Access
• [Journal Article] An Older Thrombus Delays Reperfusion after Mechanical Thrombectomy for Ischemic Stroke (2021)
  • Author(s): Kitano Takaya、Hori Yumiko、Okazaki Shuhei、Murayama Shigeo、Morii Eiichi、Sakaguchi Manabu、Yagita Yoshiki、Shimazu Takeshi、Mochizuki Hideki、Todo Kenichi
  • Journal Title: Thrombosis and Haemostasis Volume: 122 Issue: 03 Pages: 415-426
  • DOI: 10.1055/a-1522-4507
  • Peer Reviewed / Open Access
• [Journal Article] Lemur tail kinase 1 (LMTK1) regulates the endosomal localization of β-secretase BACE1 (2021)
  • Author(s): Komaki Keisuke、Takano Tetsuya、Sato Yutaka、Asada Akiko、Ikeda Shikito、Yamada Kaoru、Wei Ran、Huo Anni、Fukuchi Aoi、Saito Taro、Ando Kanae、Murayama Shigeo、Araki Wataru、Kametani Fuyuki、Hasegawa Masato、Iwatsubo Takeshi、Tomomura Mineko、Fukuda Mitsunori、Hisanaga Shin-ichi
  • Journal Title: The Journal of Biochemistry Volume: 170 Issue: 6 Pages: 729-738
  • DOI: 10.1093/jb/mvab094
  • Peer Reviewed
• [Journal Article] An autopsy report of a familial amyotrophic lateral sclerosis case carrying <scp> <i>VCP</i> Arg487His </scp> mutation with a unique <scp>TDP‐43</scp> proteinopathy (2021)
  • Author(s): Matsubara Tomoyasu、Izumi Yuishin、Oda Masaya、Takahashi Masatoshi、Maruyama Hirofumi、Miyamoto Ryosuke、Watanabe Chigusa、Tachiyama Yoshiro、Morino Hiroyuki、Kawakami Hideshi、Saito Yuko、Murayama Shigeo
  • Journal Title: Neuropathology Volume: 41 Issue: 2 Pages: 118-126
  • DOI: 10.1111/neup.12710
  • Peer Reviewed / Open Access
• [Journal Article] Cerebral large artery stenosis and occlusion in POEMS syndrome. (2021)
  • Author(s): Sugiyama A, Yokota H, Misawa S, Mukai H, Sekiguchi Y, Koide K, Suichi T, Matsushima J, Kishimoto T, Tanei ZI, Saito Y, Ito S, Kuwabara S.
  • Journal Title: BMC Neurol Volume: 21 Issue: 1 Pages: 239-239
  • DOI: 10.1186/s12883-021-02260-2
  • Peer Reviewed / Open Access
• [Journal Article] Amyotrophic lateral sclerosis with speech apraxia, predominant upper motor neuron signs, and prominent iron accumulation in the frontal operculum and precentral gyrus (2021)
  • Author(s): Mitani Tomoki T.、Beck Goichi、Kido Kansuke、Yamashita Rika、Yonenobu Yuki、Ogawa Takuya、Saeki Chizu、Okuno Tatsusada、Nagano Seiichi、Morii Eiichi、Hasegawa Masato、Saito Yuko、Murayama Shigeo、Mochizuki Hideki
  • Journal Title: Neuropathology Volume: 41 Issue: 4 Pages: 324-331
  • DOI: 10.1111/neup.12763
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Coexistence of neuronal intranuclear inclusion disease and amyotrophic lateral sclerosis: an autopsy case (2021)
  • Author(s): Sugiyama Atsuhiko、Takeda Takahiro、Koide Mizuho、Yokota Hajime、Mukai Hiroki、Kitayama Yoshihisa、Shibuya Kazumoto、Araki Nobuyuki、Ishikawa Ai、Isose Sagiri、Ito Kimiko、Honda Kazuhiro、Yamanaka Yoshitaka、Sano Terunori、Saito Yuko、Arai Kimihito、Kuwabara Satoshi
  • Journal Title: BMC Neurology Volume: 21 Issue: 1 Pages: 239-239
  • DOI: 10.1186/s12883-021-02306-5
  • Peer Reviewed
• [Journal Article] Specific gene expression in unmyelinated dorsal root ganglion neurons in nonhuman primates by intranerve injection of adeno-associated virus 6 vector. (2021)
  • Author(s): Kudo M, Wupuer S, Fujiwara M, Saito Y, Kubota S, Inoue K, Takada M, Seki K
  • Journal Title: Molecular Therapy - Methods & Clinical Development Volume: 23 Pages: 11-22
  • DOI: 10.1016/j.omtm.2021.07.009
  • Peer Reviewed / Open Access
• [Journal Article] ELISA Evaluation of Tau Accumulation in the Brains of Patients with Alzheimer Disease (2021)
  • Author(s): Shinohara Mitsuru、Hirokawa Junko、Shimodaira Akemi、Tashiro Yoshitaka、Suzuki Kaoru、Gheni Ghupurjan、Fukumori Akio、Matsubara Tomoyasu、Morishima Maho、Saito Yuko、Murayama Shigeo、Sato Naoyuki
  • Journal Title: Journal of Neuropathology &amp; Experimental Neurology Volume: 80 Issue: 7 Pages: 652-662
  • DOI: 10.1093/jnen/nlab047
  • Peer Reviewed
• [Journal Article] Distinct phosphorylation profiles of tau in brains of patients with different tauopathies. (2021)
  • Author(s): Samimi, N., Sharma, G., Kimura, T., Matsubara, T., Huo, A., Saito, S., Murayama, M., Akatsu, H., Hashizume, Y., Hasegawa, M., Farjam, M., Shahpasand, K., Ando, K., Hisanaga, S.
  • Journal Title: Neurobiol. Aging Volume: 108 Pages: 72-79
  • DOI: 10.1016/j.neurobiolaging.2021.08.011
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Neuropathy/intranuclear inclusion bodies in oculopharyngodistal myopathy: A case report (2021)
  • Author(s): Matsubara Tomoyasu、Saito Yuko、Kurashige Takashi、Higashihara Mana、Hasegawa Fumio、Ogasawara Masashi、Iida Aritoshi、Nishino Ichizo、Adachi Tadashi、Kubota Akatsuki、Murayama Shigeo
  • Journal Title: eNeurologicalSci Volume: 24 Pages: 100348-100348
  • DOI: 10.1016/j.ensci.2021.100348
  • Peer Reviewed / Open Access
• [Journal Article] Seeded assembly in vitro does not replicate the structures of α‐synuclein filaments from multiple system atrophy (2021)
  • Author(s): Lovestam Sofia、Schweighauser Manuel、Matsubara Tomoyasu、Murayama Shigeo、Tomita Taisuke、Ando Takashi、Hasegawa Kazuko、Yoshida Mari、Tarutani Airi、Hasegawa Masato、Goedert Michel、Scheres Sjors H. W.
  • Journal Title: FEBS Open Bio Volume: 11 Issue: 4 Pages: 999-1013
  • DOI: 10.1002/2211-5463.13110
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Lewy pathology of the submandibular gland in Lewy body disease: A report of autopsy cases (2021)
  • Author(s): Sakashita Yasuhiro、Matsubara Tomoyasu、Takata Tadayuki、Tanei Zen‐ichi、Motoda Atsuko、Yamazaki Mikihiro、Kawakami Ito、Sengoku Renpei、Saito Yuko、Arai Tomio、Yamada Masahito、Murayama Shigeo
  • Journal Title: Neuropathology Volume: 41 Issue: 6 Pages: 476-483
  • DOI: 10.1111/neup.12772
  • Peer Reviewed
• [Journal Article] Case report of anorexia nervosa showing periventricular gliosis at autopsy (2021)
  • Author(s): Umeda Kentaro、Kawakami Ito、Ikeda Kenji、Tanei Zen‐ichi、Matsubara Tomoyasu、Murayama Shigeo、Murahashi Yuki、Niizato Kazuhiro、Oshima Kenichi、Iritani Shuji
  • Journal Title: Neuropathology Volume: 41 Issue: 2 Pages: 127-132
  • DOI: 10.1111/neup.12711
  • Peer Reviewed
• [Journal Article] Diffusion-Weighted Imaging is Key to Diagnosing Specific Diseases (2021)
  • Author(s): Tokumaru Aya Midori、Saito Yuko、Murayma Shigeo
  • Journal Title: Magnetic Resonance Imaging Clinics of North America Volume: 29 Issue: 2 Pages: 163-183
  • DOI: 10.1016/j.mric.2021.02.001
  • Peer Reviewed
• [Journal Article] Parkinson’s disease with a typical clinical course of 17 years overlapped by Creutzfeldt?Jakob disease: an autopsy case report (2021)
  • Author(s): Kubo Shin-ichiro、Matsubara Tomoyasu、Taguchi Takeshi、Sengoku Renpei、Takeuchi Atsuko、Saito Yuko
  • Journal Title: BMC Neurology Volume: 21 Issue: 1 Pages: 480-480
  • DOI: 10.1186/s12883-021-02504-1
  • Peer Reviewed / Open Access
• [Presentation] 2021 annual report of Brain Bank for Aging Research (2021)
  • Author(s): Murayama S, Saito Y
  • Organizer: 2021 AANP Annual Meeting
  • Int'l Joint Research