一般口演
優秀演題賞候補（病理） |
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| 7月6日（木） 15:00-16:30 Room B
1O⑨-1
DNA methylation states of neurons and oligodendrocyte lineage cells in human postmortem brain
林 義剛1, 中林 一彦2, 郷 康広3, 一杉 正仁4, 等 誠司1
1. 滋賀医科大学 統合臓器生理学, 2. 国立成育医療研究センター 周産期病態研究部 周産期ゲノミクス研究室, 3. 自然科学研究機構 生命創成探究センター 認知ゲノム研究グループ, 4. 滋賀医科大学 法医学部門
Yoshitaka Hayashi1, Kazuhiko Nakabayashi2, Yasuhiro Go3, Masahito Hitosugi4, Seiji Hitoshi1
1. Dept. of Integrative Physiology, Shiga Univ Med Sci, Shiga, Japan, 2. Dept. of Maternal Fetal Biology, National Center for Child Health and Development, 3. Exploratory Research Center on Life and Living Systems (ExCELLS), National Institutes of Natural Sciences, 4. Dept. of Legal Medicine, Shiga Univ Med Sci
DNA methylation analysis of postmortem brain performed on cortical gray matter, but it is unclear whether the results reflect pathology or differences in cell density of brain. Therefore, cell type-specific analysis is important to investigate epigenetic differences in the brain. In this study, cell nuclei are extracted from two human postmortem brains and stained for NeuN, a marker for neurons, and Olig2, a marker for oligodendrocyte lineage cells. Then those positive cells were sorted by a cell sorter and DNA was extracted. The methylation state of the DNA was comprehensively analyzed by the Reduced Representation Bisulfite Sequencing method using a next-generation sequencer. Comparison of neuron-oligodendrocyte lineage cells showed synaptic signaling-related, learning, and memory-related genes were hypomethylated in the neurons and myelin-related genes and glial cells differentiation genes were hypomethylated in the oligodendrocyte lineage cells. In the oligodendrocyte-oligodendrocyte progenitor cell comparison, oligodendrocytes were hypomethylated for myelin- and myelination-related genes, whereas oligodendrocyte progenitor cells were, interestingly, hypomethylated for genes related to neurogenesis and cell differentiation inhibition. We consider these results to be fundamental data for the human brain and neurological diseases. | | 7月6日（木） 15:00-16:30 Room B
1O⑨-2
Gordon Holmes syndrome and SCA17-DI: pathology of 2 unrelated patients with Huntington-like disorder
齋藤 理恵1, 多田 有似2, 及川 大輔3, 佐藤 裕介4, 岩永 圭介5,6, 佐藤 聡5, 瀬戸 牧子5, 久米 広大2, 上木 望7, 中島 正洋7, 林 森太郎1,8, 豊島 靖子1,9, 徳永 文稔3, 川上 秀史2, 柿田 明美1
1. 新潟大学脳研究所病理学分野，新潟市，日本, 2. 広島大学原爆放射線医科学研究所分子疫学研究分野, 3. 大阪公立大学大学院医学研究科分子病態学, 4. 鳥取大学工学部化学バイオ系学科, 5. 長崎北病院神経内科, 6. 油木坂クリニック, 7. 長崎大学原爆後障害医療研究所腫瘍診断病理学研究分野, 8. 三島病院神経内科, 9. 阿賀野病院脳神経内科
Rie Saito1, Yui Tada2, Daisuke Oikawa3, Yusuke Sato4, Keisuke Iwanaga5,6, Akira Satoh5, Makiko Seto5, Kodai Kume2, Nozomi Ueki7, Masahiro Nakashima7, Shintaro Hayashi1,8, Yasuko Toyoshima1,9, Fuminori Tokunaga3, Hideshi Kawakami2, Akiyoshi Kakita1
1. Dept. of Pathol., B. R. I., Niigata Univ., Niigata, Japan
Object: To clarify the pathologic and genetic features in 2 families with Huntington-like disorder.
Method: We examined histopathologically the brains of 2 patients (a male aged 66 years, patient 1; and a female aged 75 years, patient 2) from different families with Huntington-like disorder (HLD) including chorea and dementia, and cerebellar recessive ataxia. Whole-exome sequencing was performed.
Results: Histopathologically, both patients had similar features of degeneration, including severe loss of Purkinje cells, and moderate neuronal loss with gliosis in the caudate nucleus and inferior olivary nucleus. Neuronal loss was also seen in the frontal and motor cortices, where the white matter showed diffuse myelin pallor. On the other hand, neuronal accumulation of CAG aggregates was observed in the CNS of patient 2, but not in patient 1. Genetic analysis revealed a novel homozygous mutation, Y482H in RNF216, a known cause of Gordon Holmes syndrome (GHS) with hypogonadism and cerebellar recessive ataxia in patient 1, and an intermediate allele (41 and 38 CAG/CAA repeats) in TBP and a heterozygous missense mutation in STUB1 (p.P243L), establishing a diagnosis of SCA17-digenic inheritance (SCA17-DI) in patient 2.
Conclusion: Our findings clarify the clinicopathologic characteristics of GHS and SCA17-DI. When encountering patients with HLD, GHS and SCA17-DI should be considered. | | 7月6日（木） 15:00-16:30 Room B
1O⑨-3
Cryo-electron microscopic analysis reveals microtubule shoots triggers in microtubule-stabilized axonal regeneration
平 賢一郎1,2, Yurika Yamada1, Satish Bodakuntla1, King Cada1, Nirakar Basnet3, Hana Nedozralova4, Christian Biertumpfel1, Naoko Mizuno1
1. アメリカ国立衛生研究所, 2. 東京都健康長寿医療センター 脳神経内科, 3. Institute for protein innovation, Cambridge, Massachusetts, 4. Central European Institute of Technology
Kenichiro Taira1,2, Yurika Yamada1, Satish Bodakuntla1, King Cada1, Nirakar Basnet3, Hana Nedozralova4, Christian Biertumpfel1, Naoko Mizuno1
1. Laboratory of Structural Cell Biology, National Heart, Lung, and Blood Institute, National Institutes of Health, 2. Department of Neurology, Tokyo Metropolitan Geriatric Hospital and Institution of Gerontology, 3. Institute for protein innovation, Cambridge, Massachusetts, 4. Central European Institute of Technology
Objectives: To show molecular mechanism of microtubule-stabilized axonal regeneration in central nervous system at early stages using cryo-electron microscopy (cryo-EM). Methods: Thalamus explants were prepared from mice embryos. Distal axonectomy as a model of axonal injury was a process of cutting and clearing away distal parts using a micro needle. Injured axons treated with 1 nM of Epothilone B (EpoB), as a microtubule-stabilizing drug, were compared with those without EpoB. Cryo-EM analysis includes as follows: (1) montage images ; (2) tomoraphy taken; (3) microtubules snapshots by single-particle analysis (SPA). Results: On cryo-EM analysis, membrane closure happened immediately after axonectomy. Without EpoB, most axons degenerated with membranes forming bubble-like entities sealing cellular components. However, treated with epoB, bundles of microtubules shot out from the injured site with breaking membrane seal and abundant vesicular trafficking. The length of exposed microtubules reached around 20 μm beyond the injury site. SPA revealed that microtubules were physiological assembled with 13 protofilaments and the orientations were aligned with the plus ends (5.5 Angstrom). The inner lumen part showed EpoB density at the binding pocket.Conclusion: Shooting-out microtubules occurred without membrane coverage at early stages of axonal regeneration on cryo-EM analysis. | | 7月6日（木） 15:00-16:30 Room B
1O⑨-4
量子ドットの金増感によるヒト剖検標本の二重光電子相関顕微鏡法（CLEM）
Dual correlative light and electron microscopy (CLEM) of human autopsy specimens by gold enhancement of quantum dots
植松 未帆1,6, 三上 恭平2, 中村 綾子1,3, 横田 隆徳3, 廣川 勝いく4, 内原 俊記1,3,5
1. 東京都医学総合研究所脳病理形態研究室, 2. 東京都医学総合研究所ヒストロジー支援室, 3. 東京医科歯科大学大学院医歯学総合研究科脳神経病態学分野, 4. 新渡戸記念中野総合病院病理診断科, 5. 新渡戸記念中野総合病院脳神経内科, 6. 大阪公立大学大学院医学研究科ゲノム免疫学
Miho Uematsu1,6, Kyohei Mikami2, Ayako Nakamura1,3, Takanori Yokota3, Katsuiku Hirokawa4, Toshiki Uchihara1,3,5
1. Structural Neuropathology, Tokyo Metropolitan Institute of Medical Science, 2. Histology Center, Tokyo Metropolitan Institute of Medical Science, 3. Dept. of Neurology and Neurological Science, Tokyo Medical and Dental Univ., 4. Dept. of Pathology, Nitobe Memorial Nakano General Hospital, 5. Dept. of Neurology, Nitobe Memorial Nakano General Hospital, 6. Dept. of Immunology and Genomics, Osaka Metropolitan Univ.
Cadmium selenide quantum dots (QDs) are fluorescent and electron-dense nanoparticles that, when used as reporters for immunolabeling, allow direct comparison of fluorescent signals on light microscopy (LM) and ultrastructure on electron microscopy (EM) as correlated light and electron microscopy (CLEM). In this study, QD particles on the EM grid were enhanced with gold to increase the electron density of the particles. The rod-shaped QD655 was gold enhanced at both ends of the particle, whereas the spherical QD565 was gold enhanced spherically, so that QDs with different original shapes could be more clearly distinguished on EM by the different gold enhancement patterns. This distinction by EM was also clear in tissue sections double immunolabeled with QD565 (green fluorescence) and QD655 (red fluorescence) as reporter pairs, and mutual comparison of LM and EM confirmed the specific labeling of each epitope. Target structures labeled with gold-enhanced QDs were identifiable by brightfield microscopy due to their coloration, which facilitated trimming of the target structure on the final EM sections. Double labeling CLEM with gold-enhanced QDs is a simple and feasible strategy that does not require special equipment. This method can be applied to formalin-fixed human brain samples and paves the way to investigate how different molecules are woven into complex ultrastructure. | | 7月6日（木） 15:00-16:30 Room B
1O⑨-5
Histopathological characteristics of patients with late-onset multiple system atrophy
小澤 美里1,2, 齋藤 理恵1, 今野 卓哉3, 池田 哲彦4, 横関 明男5, 谷 卓6, 黒羽 泰子6, 小出 玲爾2, 藤本 茂2, 小野寺 理3, 柿田 明美1
1. 新潟大学脳研究所 病理学分野, 2. 自治医科大学内科学講座 神経内科学部門, 3. 新潟大学脳研究所 脳神経内科, 4. 国立病院機構新潟病院 脳神経内科, 5. 脳神経センター阿賀野病院 脳神経内科, 6. 国立病院機構西新潟中央病院 脳神経内科
Misato Ozawa1,2, Rie Saito1, Takuya Konnno3, Tetsuhiko Ikeda4, Akio Yokoseki5, Takashi Tani6, Yasuko Kuroha6, Reiji Koide2, Shigeru Fujimoto2, Osamu Onodera3, Akiyoshi Kakita1
1. Department of Pathology, Brain Research Institute, Niigata University, Niigata, Japan
Objective: Despite the recognition of late-onset multiple system atrophy (LO-MSA), details of its histopathological features remain unknown. This study aimed to clarify the histopathological characteristics of LO-MSA.
Methods: We retrieved 4 autopsied patients with LO-MSA (age at onset ≧75 years) and 24 patients with usual-onset (UO)-MSA (age at onset 55-65) with a disease duration similar to that of LO-MSA. We semiquantitatively assessed the severity of degeneration in the SN and OPC systems. Immunohistochemically, we counted the numbers of tryptophan hydroxylase-positive serotonergic neurons in the ventrolateral nucleus of the medulla (VLM) and nucleus raphe obscurus, and choline acetyltransferase-positive cholinergic neurons in the intermediolateral nucleus.
Results: Both groups mostly corresponded to the OPCA type. Degeneration of the SN and OPC systems in LO-MSA tended to be milder than in UO-MSA. When restricted to OPCA-type patients, the grades of degeneration of SN and total SN and OPC in LO-MSA were significantly lower than those in UO-MSA (1±0, 1.74±0.56, P＜0.05, 3.67±0.58 vs.4.6±0.70, P＜0.05). The number of serotonergic neurons in the VLM of LO-MSA patients remained significantly higher than in UO-MSA patients (4.33±1.53 vs.1.50±1.35, P＜0.01).
Conclusion: The degeneration of the SN and autonomic systems in LO-MSA may progress more mildly than that in UO-MSA. | | 7月6日（木） 15:00-16:30 Room B
1O⑨-6
Neuropathologic characteristics and cellular alterations of patients with long-duration multiple system atrophy
中原 亜紗1, 他田 真理1, 池田 哲彦2, 中島 孝2, 黒羽 泰子3, 野崎 洋明4, 佐藤 晶4, 小野寺 理5, 柿田 明美1
1. 新潟大学脳研究所 病理, 2. 国立病院機構 新潟病院 脳神経内科, 3. 国立病院機構 西新潟中央病院 脳神経内科, 4. 新潟市民病院 脳神経内科, 5. 新潟大学脳研究所 脳神経内科
Asa Nakahara1, Mari Tada1, Tetsuhiko Ikeda2, Takashi Nakajima2, Yasuko Kuroha3, Hiroaki Nozaki4, Aki Sato4, Osamu Onodera5, Akiyoshi Kakita1
1. Dept. Pathol., Brain Res. Inst. Niigata Univ., 2. Dept. Neurol., NHO Niigata Natl. Hosp., 3. Dept. Neurol., NHO Nishiniigata Chuo Hosp., 4. Dept. Neurol., Niigata City General Hosp., 5. Dept. Neurol., Brain Res. Inst. Niigata Univ.
【Objective】To clarify the neuropathologic characteristics and cellular alterations of patients with long-duration multiple system atrophy (MSA).
【Methods】We retrieved 10 consecutive autopsy-proven cases of MSA with a disease duration of >15 years (MSA-long: MSA-L). The amounts of phosphorylated α-synuclein (αsyn)- and tau-immunoreactive (ir) neuronal and glial cytoplasmic inclusions (NCIs and GCIs) in the prefrontal cortex and white matter, amygdala, Ammon’s horn, and dentate gyrus were assessed semi-quantitatively in comparison with 8 MSA cases of 7 years duration (MSA-median: MSA-M). The clinical diagnosis was MSA in all cases.
【Results】The amounts of αsyn-ir GCIs in the prefrontal white matter and cortex were significantly higher in MSA-L than in MSA-M (p<0.05). All MSA-L and 4 MSA-M cases also had tau-ir GCIs in those areas, and the amount in MSA-L was significantly higher than that in MSA-M (p<0.05). All MSA-L cases had plump GCIs, and 6 cases had GCIs with granulovacuolar change. The amounts of αsyn-ir NCIs in the amygdala and dentate gyrus were significantly higher in MSA-L than in MSA-M (p<0.05). Pick body-like αsyn-ir NCIs were seen in 6 MSA-L cases, but in only one MSA-M case.
【Conclusion】Cases of MSA-L may be characterized by certain features, including expansion of cellular αsyn aggregates into the frontotemporal lobes, plump inclusions and tau co-aggregation. | | 7月6日（木） 15:00-16:30 Room B
1O⑨-7
Distinct characteristics of limbic-predominant age-related TDP-43 encephalopathy in Lewy body disease
上村 麻衣子1,2, 高橋 良輔1, Virginia Lee2, Edward Lee2
1. 京都大学 大学院医学研究科 脳病態生理学講座臨床神経学講座, 2. ペンシルベニア大学神経変性疾患研究センター
Maiko Uemura1,2, Ruosuke Takahashi1, Virginia Lee2, Edward Lee2
1. Dept. of Neurol., Graduate School of Medicine, Kyoto Univ., Kyoto, Japan
Distinct characteristics of limbic-predominant age-related TDP-43 encephalopathy in Lewy body disease
1. Department of Neurology, Kyoto University Graduate School of Medicine
2. Center for Neurodegenerative Disease Research (CNDR), Perelman School of Medicine at the University of Pennsylvania
Objective
We aimed to identify the pathological, clinical, and genetic characteristics of LATE in LBD (LATE-LBD).
Methods
We assessed the association of LATE with patient profiles in the cohorts of LBD (n=313), AD (n=282), LBD+AD (n=355), and Aging (n=111). We studied the neuropathological differences between LATE-LBD and LATE-AD. By frequency analysis, we staged LATE-LBD and examined the association with cognitive impairment and genetic risk factors.
Results
The frequency of LATE was the highest in LBD+AD, followed by AD, LBD, and Aging, and that was associated with LBD subtype and AD neuropathologic change. The hippocampal distribution of LATE was different between LATE-LBD and LATE-AD, and abundant fine neurites were found in LATE-LBD. LATE spreading pattern was also different between LATE-LBD and LATE-AD. The presence and prevalence of LATE in LBD were associated with cognitive impairment; the LATE-LBD stage was also associated with the genetic risk variants of TMEM106B rs1990622 and GRN rs5848.
Conclusion
These data highlight clinicopathological and genetic features of LATE-LBD. | | 7月6日（木） 15:00-16:30 Room B
1O⑨-8
FTLD-TDP presenting as atypical parkinsonism
村上 綾1,2, 古賀 俊輔2, Nicholas B. Martin2, 関谷 博顕2, Dennis W. Dickson2
1. 関西医科大学 脳神経内科, 2. メイヨークリニック 神経科学部門
Aya Murakami1,2, Shunsuke Koga2, Nicholas B. Martin2, Hiroaki Sekiya2, Dennis W. Dickson2
1. Department of Neurology, Kansai Medical University, Osaka, Japan, 2. Department of Neuroscience, Mayo Clinic, Jacksonville, Florida, USA
Objective: The clinical manifestations of frontotemporal lobar degeneration with TDP-43 pathology (FTLD-TDP) are often associated with semantic dementia, behavioral variant frontotemporal dementia, and progressive non-fluent aphasia. There are, however, relatively few reports of atypical parkinsonism caused by FTLD-TDP. We aimed to describe the clinicopathological features of patients with FTLD-TDP presenting as atypical parkinsonism.Methods: A brain bank for neurodegenerative disease was queried for cases with FTLD-TDP pathology. All brains underwent systematic and standardized neuropathologic evaluation, including tau and TDP-43 immunohistochemistry. Clinical information was extracted from medical records.Results: We found 270 patients with FTLD-TDP. Of those, 13 were clinically diagnosed with atypical parkinsonian disorders, such as corticobasal syndrome (CBS; n=7) and progressive supranuclear palsy (PSP; n=6). The average age at onset and disease duration was 70 ± 8 years and 7 ± 3 years, respectively. The average brain weight was 972 ± 141 grams. The median Braak neurofibrillary tangle stage was II, and Thal amyloid phase was 1. The subtype of TDP-43 pathology was Type A in 10 and type B in 3 patients.Conclusions: Patients with FTLD-TDP can clinically mimic CBS and PSP; therefore, FTLD-TDP should be considered in the differential diagnosis of atypical parkinsonism. | | 7月6日（木） 15:00-16:30 Room B
1O⑨-9
Pathological background of decreased CSF Aβ42 in dementia with Lewy bodies and progressive supranuclear palsy
栗原 正典1,2, 松原 知康3, 金丸 和富1, 岩田 淳1,2, 齊藤 祐子3, 村山 繁雄3,4
1. 東京都健康長寿医療センター 脳神経内科, 2. 東京都健康長寿医療センター 認知症未来社会創造センター, 3. 東京都健康長寿医療センター 神経病理学 (高齢者ブレインバンク), 4. 大阪大学 大学院連合小児発達学研究科附属子どものこころの分子統御機構研究センター ブレインバンク・バイオリソース部門
Masanori Kurihara1,2, Tomoyasu Matsubara3, Kazutomi Kanemaru1, Atsushi Iwata1,2, Yuko Saito3, Shigeo Murayama3,4
1. Department of Neurology, Tokyo Metropolitan Geriatric Hospital and Institute of Gerontology, 2. Integrated Research Initiative for Living Well with Dementia, Tokyo Metropolitan Geriatric Hospital and Institution of Gerontology, 3. Department of Neuropathology (Brain Bank for Aging Research), Tokyo Metropolitan Geriatric Hospital and Institute of Gerontology, 4. Brain Bank for Neurodevelopmental, Neurological and Psychiatric Disorders, United Graduate School of Child Development, Osaka University
Background: Cerebrospinal fluid amyloid-beta 42 (CSF Aβ42) decreases in Alzheimer’s disease (AD) likely due to consumption of soluble Aβ42 in brain amyloid plaques. Although CSF Aβ42 can also be decreased in dementia with Lewy bodies (DLB)/Parkinson’s disease with dementia (PDD) or progressive supranuclear palsy (PSP), the neuropathological background remains undetermined. Methods: Patients with available antemortem CSF Aβ42 results and neuropathological assessment at autopsy were retrospectively evaluated. Diagnoses were based on postmortem pathology. CSF Aβ42 was measured by ELISA and predetermined cut-off of 500 pg/mL was used. AD pathology was evaluated according to current guidelines. Results: Results were available from 20 patients with DLB/PDD and 19 patients with PSP. CSF Aβ42 was below cut-off in 10 (50%) with DLB/PDD and 11 (58%) with PSP. While CSF Aβ42 was decreased as postmortem neuropathological amyloid stages increase in DLB/PDD, decreased CSF Aβ42 was observed in PSP patients without brain amyloid pathology. Discussion: Recent studies suggest that CSF Aβ42/Aβ40 ratio is more specific for brain amyloid pathology. Further studies are warranted to evaluate whether CSF Aβ42/Aβ40 can estimate brain amyloid pathology in patients with PSP. Conclusion: CSF Aβ42 predicts brain amyloid pathology in patients with DLB but not necessarily in those with PSP. | | | |
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