AOCN2021 @ Taipei

The Brain Bank Project
to conquer intractable disorders-

Asian- Oceanian Network
Specially Appointed Professor,
Brain Bank for Neurodevelopmental,
Neurological and Psychiatric Disorders,
United Graduate School of Child Development,
Osaka University

Shigeo Murayama M.D. Ph.D.

1

My Background• I am a Buddhist priest of Soto school of Zen(曹洞宗）.
• I have been educated that those who haveeaten food offered to Buddha （仏飯）should
dedicate their life to all living creatures on
earth（衆生）.
• To establish all Japan Brain Bank Network is
my life work, which I interpret to be
Bodhisattva line（菩薩行）.
• I will go anywhere to fulfill brain donors’ will or
guide doctors who want to contribute to brainbanking.
My background a buddhist.

2

COI
President, the Asian Oceanian Society of Neuropathology,
Vice President: the International Society of Neuropathology,
Honorable Member: the Japanese Societies of Neurology,
Neuropathology and Dementia Research
Associate Editor, JNEN
Visiting Professor: Tokushima, Hiroshima, Tokyo Medical,
Doshisha and Osaka City Universities;
Neuropathology Consultant: NCGG, Kagawa University;
NHO Tokyo, Shimoshizu, Shizuoka Epilepsy and Neurology,
West Hiroshima and Okinawa Hospitals; Kameda,
Yokohama Rosai, Toranomon, NTT East Kanto andChikamori Hospitals

My COI.

3

The Brain Bank for Aging Research (BBAR)
TMGHIG

Resources consisting of consecutive
autopsy cases from a general geriatrichospital & all Japan depository of rareneurological and developmental
disorders (http://www.mci.gr.jp/BrainBank)

In House Cohort Resource
1. Paraffin blocks and glass slides (1972.5-)
for Clinical, Radiological and Pathological Research 7418
>2. Frozen neocortex and body tissues (1995.1-)
for Molecular Research: 2,415>3. Frozen half brains (2001.7- )for Neuroscience Research: 1,102
All Japan Neurological and Developmental Depository
In collaboration with Brain Bank for Neurodevelopmental,
Neurological and Psychiatric Disorders (BBNNPD)

The Brain Bank for Aging Research has been accumulating paraffin blocks ofbrain and body tissues since 1972, frozen small pieces of brain and body tissues
since 1995 and frozen half brains, spinal cords and peripheral autonomic nervous
tissues since 2001. We are also responsible for all Japan depository of rare
intractable neurological disorders.

4The Brain Bank for Aging Research (BBAR)
Tokyo Metropolitan Geriatric Hospital & Institute of Gerontology
Brain Bank is a movement conducted by patients, doctors andresearchers, to conquer intractable neuro- psychiatric disorders.
Kazutomo Imahori
Neurology

Clinical Branch

Pathology

Tokyo Metropolitan
Geriatric Hospital
Clinical CenterTokyo Metropolitan Geriatric
Hospital & Institute ofGerontology
Tokyo Metropolitan Instituteof Gerontology

Administrative OfficeTranslational
Research

Geriatric Pathology
Research

The Brain Bank forAging Research

The Biobank forAging Research

Neuropathology

The Brain Bank for Aging Research is a cooperative center of both the hospitaland the research institute and supported by the Departments of Neurology and
Neuropathology.

5

2020 Collaboration
PI

Institutewww.mci.gr.jp/BrainBank/

Research theme

1 Ikeuchi, K.

NIBR

2 Kuwano, R.

NIBR

miRNA editing in Alzheimer brain

3 Toda, T.

Kobe Univ.

Genomic pathology of neurological disease

apoE4 and aging brain

4 Nishimura, M.

Mol. Neurosci. Shiga Med. Univ. Novel protein in human aging

5 Hasegawa, M.

Tokyo Metro. Inst. Med. Sci.

CSF early biomarker of AD

6 Ono, M.

Pharm . Shiga Med. Univ.

Estrogen receptor in AD

7 Hisanaga, S.

Tokyo Metro. Univ.

Tau phosphorylation in tauopathy

8 Takahashi, Y.

Neurol. NCNP

Immunocytochemistry of ALS

Enviro. Res. Nagoya Univ.

Novel biomarker in neurodegeneration

9 Yamanaka, K.
10 Ito, M.

TMGHIGSiRNA in argyrophilic grain disease

11 Okamura, N.

Tohoku Pharm. Univ.

Pet ligand for tau and alpha- synuclein

12 Miyasaka, T.

Life Sci. Doshisha Univ.

Imaging m ass spectroscopy of human brain

13 Tanaka, M.

Riken

DISC1 and neurodegeneration

14 Tsuji, S.

Neurol. UT

15 Ishikawa, K.

Neurol. TMDU

Genomic screening of ACA

16 Iwata, A.

Neurol. UT

Epigenetics of ALS

Genomic screening in neurodegeneration

17 Tokum aru, A.

Raidiol. TMGHIG

18 Hattori, N.

Neurol. Junten. Univ.

Genomic screening of PD

19 Kwak, S.

Neurol. UTRNA editing in ALS

20 Kubo, S.

W hite matter change in MRI

Neurol. Junten. Univ.

Back ground pathology of early LBD

21 Okazawa, H.

Neuropath. TMDU

Proteomic analysis of neurodeneratiion.

22 Kokubo, Y.

Mie Univ.

ALS/PDC Kii

23 Higuchi, M.

NIRS

alpha- synuclein ligand

24 Honma, N.

Patho. Toho Univ.

Estrogen receptor in AD

25 Hashimoto, Y.

Fukushima Med. Univ.

26 Sengoku, R.

Neurol. TMGHIG

Pathology of olfactory plate

27 Hashimoto, K.

Psy. Res. Cntr. Chiba Univ.

Lipid metabolism in PD

28 Saito, Y.

Life Sci. Doshisha Univ.

Glycosylation in AD

anti- oxidant DJ1 in LBD

29 Kato, T.

Riken

Neuropathology of depression

30 Nagata, N.

Animal Radiol. UT

L-PGDS in NPH

31 Kabuta, T.

NCNP

32 Sato, N.

NCGG

DM and demntia

33 Ri, M.

Juntendo Univ.

CHCHD2 gene in neurodegeneration

Pet Center TMGHIG

Neuropathology of tau imaging

34 Ishii, K.

Chaperone- mediated autophagy

35 Imaizumi, K.

Hiroshima Univ.

ER stress

36 Nagai, Y.

Osaka Univ.

exom e analysis of in vivo proteostasis

37 Araki, I.

NCNP

BACE1 and synapse degeneration in AD

38 Yam agoshi, T.

NCGG

Salivary gland in aging

39 Kameyama, A.

AISTGlycomics in aging

40 Ishigami, A.

TMGHIG

Citrulinated protein as an early biomarker of AD

41 Suhara, T.

NIRS

Dynamic pathology of amyloid- negative dem entia

42 Ishiura, H.

Neurol. UTHigh grade genom e study of neurodegeneration

BBAR provided its resource to 42 laboratories in 2020.

6

2020 publication[1] Hamaguchi T, Sakai K, Kobayashi A, Kitamoto T, Ae R, Nakamura Y, Sanjo N, Arai K, Koide M, Katada F, Harada M, Murai H, Murayama S, Tsukamoto T, Mizusawa H,
Yamada M: Characterization of Sporadic Creutzfeldt-Jakob Disease and History of Neurosurgery to Identify Potential Iatrogenic Cases. Emerg Infect Dis 2020, 26:1140-6.
[2] Hamaguchi T, Sanjo N, Ae R, Nakamura Y, Sakai K, Takao M, Murayama S, Iwasaki Y, Satoh K, Murai H, Harada M, Tsukamoto T, Mizusawa H, Yamada M: MM2-type
sporadic Creutzfeldt-Jakob disease: new diagnostic criteria for MM2-cortical type. J Neurol Neurosurg Psychiatry 2020.
[3] Hata S, Hu A, Piao Y, Nakaya T, Taru H, Morishima-Kawashima M, Murayama S, Nishimura M, Suzuki T: Enhanced amyloid-beta generation by gamma-secretase complex in
DRM microdomains with reduced cholesterol levels. Hum Mol Genet 2020, 29:382-93.
[4] Hideshima M, Beck G, Yamadera M, Motoyama Y, Ikenaka K, Kakuda K, Tsuda H, Nagano S, Fujimura H, Morii E, Murayama S, Mochizuki H: A clinicopathological study of
ALS with L126S mutation in the SOD1 gene presenting with isolated inferior olivary hypertrophy. Neuropathology 2020, 40:191-5.
[5] Imai M, Tanaka M, Sakata M, Wagatsuma K, Tago T, Toyohara J, Sengoku R, Nishina Y, Kanemaru K, Ishibashi K, Murayama S, Ishii K: Metabolic Network Topology of
Alzheimer's Disease and Dementia with Lewy Bodies Generated Using Fluorodeoxyglucose Positron Emission Tomography. J Alzheimers Dis 2020, 73:197-207.
[6] Ishigaki K, Akiyama M, Kanai M, Takahashi A, Kawakami E, Sugishita H, Sakaue S, Matoba N, Low SK, Okada Y, Terao C, Amariuta T, Gazal S, Kochi Y, Horikoshi M, Suzuki
K, Ito K, Koyama S, Ozaki K, Niida S, Sakata Y, Sakata Y, Kohno T, Shiraishi K, Momozawa Y, Hirata M, Matsuda K, Ikeda M, Iwata N, Ikegawa S, Kou I, Tanaka T, Nakagawa H,
Suzuki A, Hirota T, Tamari M, Chayama K, Miki D, Mori M, Nagayama S, Daigo Y, Miki Y, Katagiri T, Ogawa O, Obara W, Ito H, Yoshida T, Imoto I, Takahashi T, Tanikawa C,
Suzuki T, Sinozaki N, Minami S, Yamaguchi H, Asai S, Takahashi Y, Yamaji K, Takahashi K, Fujioka T, Takata R, Yanai H, Masumoto A, Koretsune Y, Kutsumi H, Higashiyama M,
Murayama S, Minegishi N, Suzuki K, Tanno K, Shimizu A, Yamaji T, Iwasaki M, Sawada N, Uemura H, Tanaka K, Naito M, Sasaki M, Wakai K, Tsugane S, Yamamoto M,
Yamamoto K, Murakami Y, Nakamura Y, Raychaudhuri S, Inazawa J, Yamauchi T, Kadowaki T, Kubo M, Kamatani Y: Large-scale genome-wide association study in a Japanese
population identifies novel susceptibility loci across different diseases. Nat Genet 2020, 52:669-79.
[7] Kakuda N, Yamaguchi H, Akazawa K, Hata S, Suzuki T, Hatsuta H, Murayama S, Funamoto S, Ihara Y: gamma-Secretase Activity Is Associated with Braak Senile Plaque Stages.
Am J Pathol 2020, 190:1323-31.
[8] Kameyama M, Ishibashi K, Toyohara J, Wagatsuma K, Umeda-Kameyama Y, Shimoji K, Kanemaru K, Murayama S, Ogawa S, Tokumaru AM, Ishii K: Voxel-based
morphometry focusing on medial temporal lobe structures has a limited capability to detect amyloid beta, an Alzheimer's disease pathology. Aging (Albany NY) 2020, 12.
[9] Kitano T, Sakaguchi M, Yamagami H, Ishikawa T, Ishibashi-Ueda H, Tanaka K, Okazaki S, Sasaki T, Kadono Y, Takagaki M, Nishida T, Nakamura H, Yanase M, Fukushima N,
Shiozawa M, Toyoda K, Takahashi JC, Funatsu T, Ryu B, Yoshioka D, Toda K, Murayama S, Kawamata T, Kishima H, Sawa Y, Mochizuki H, Todo K: Mechanical thrombectomy inacute ischemic stroke patients with left ventricular assist device. J Neurol Sci 2020, 418:117142.
[10] Koshi-Mano K, Mano T, Morishima M, Murayama S, Tamaoka A, Tsuji S, Toda T, Iwata A: Neuron-specific analysis of histone modifications with post-mortem brains. Sci Rep
2020, 10:3767.
[11] Moriguchi S, Takahata K, Shimada H, Kubota M, Kitamura S, Kimura Y, Tagai K, Tarumi R, Tabuchi H, Meyer JH, Mimura M, Kawamura K, Zhang MR, Murayama S,
Suhara T, Higuchi M: Excess tau PET ligand retention in elderly patients with major depressive disorder. Mol Psychiatry 2020.
[12] Nagano S, Jinno J, Abdelhamid RF, Jin Y, Shibata M, Watanabe S, Hirokawa S, Nishizawa M, Sakimura K, Onodera O, Okada H, Okada T, Saito Y, Takahashi-Fujigasaki J,
Murayama S, Wakatsuki S, Mochizuki H, Araki T: TDP-43 transports ribosomal protein mRNA to regulate axonal local translation in neuronal axons. Acta Neuropathol 2020,
140:695-713.
[13] Omura T, Motoyama R, Tamura Y, Nonaka K, Tanei ZI, Shigemoto K, Tokumaru AM, Murayama S, Arai T, Araki A: Meningoencephalitis caused by masked mastoiditis thatwas diagnosed during a follow-up in an elderly patient with diabetes mellitus: A case report. Geriatr Gerontol Int 2020, 20:500-1.
[14] Schweighauser M, Shi Y, Tarutani A, Kametani F, Murzin AG, Ghetti B, Matsubara T, Tomita T, Ando T, Hasegawa K, Murayama S, Yoshida M, Hasegawa M, Scheres SHW,
Goedert M: Structures of alpha-synuclein filaments from multiple system atrophy. Nature 2020, 585:464-9.
[15] Serisawa S, Hirao K, Sato T, Ogawa Y, Kanetaka H, Enomoto M, Shimizu S, Sakurai H, Sakashita Y, Murayama S, Hanyu H: Adult-onset neuronal intranuclear inclusion disease
showing markedly high phosphorylated tau protein levels in cerebrospinal fluid. Geriatr Gerontol Int 2020, 20:793-5.
[16] Tanaka H, Homma H, Fujita K, Kondo K, Yamada S, Jin X, Waragai M, Ohtomo G, Iwata A, Tagawa K, Atsuta N, Katsuno M, Tomita N, Furukawa K, Saito Y, Saito T, Ichise A,
Shibata S, Arai H, Saido T, Sudol M, Muramatsu SI, Okano H, Mufson EJ, Sobue G, Murayama S, Okazawa H: YAP-dependent necrosis occurs in early stages of Alzheimer's disease
and regulates mouse model pathology. Nat Commun 2020, 11:507.
[17] Uchino A, Nagai M, Kanazawa N, Ichinoe M, Yanagisawa N, Adachi K, Nanba E, Ishiura H, Mitsui J, Tsuji S, Suzuki K, Murayama S, Nishiyama K: An autopsy case of GM1
gangliosidosis type II in a patient who survived a long duration with artificial respiratory support. Neuropathology 2020.
[18] Yoshinaga S, Yamanaka T, Miyazaki H, Okuzumi A, Hiyama A, Murayama S, Nukina N: Preserved proteinase K-resistant core after amplification of alpha-synuclein aggregates:
Implication to disease-related structural study. Biochem Biophys Res Commun 2020, 522:655-61.
[19] Zhang W, Tarutani A, Newell KL, Murzin AG, Matsubara T, Falcon B, Vidal R, Garringer HJ, Shi Y, Ikeuchi T, Murayama S, Ghetti B, Hasegawa M, Goedert M, Scheres SHW:
Novel tau filament fold in corticobasal degeneration. Nature 2020, 580:283-7[20]. Tanei, S., Saito, Y, …Murayama, S.: Lewy pathology of the esophagus correlates with the progression of Lewy body disease: a Japanese cohort study of autopsy cases: Lewy
pathology of the esophagus correlates with the progression of Lewy body disease: a Japanese cohort study of autopsy cases. Acta Neuropath in press

We published 20 English original peer- reviewed papers in 2020.a

7

Donor Card

Late Eameritus Professor Toyokura, the University of Tokyo and Emeritus
President of TMGHIG was the founder of our brain donation program.
“Please use my body to establish the path to cure the incurable diseases that will
kill me.” He suffered from cardiomyopathy with a mutation of myosin light chain.

8Preregistered donors who fulfilled their will（2019/5）: preregistrants: 160
N
Age Gen.
o.

Dix

IC

Place of death

80

M

（CCM）

S

FTMGHIG

2

83

M

FaAD

F

3

79

F

FaAD

F

4

69

F

CBD-PNFLA/
TDP-43 type A

F

5

86

F

AD

F

1

6

91

M

AD/CAA/DG/HS
TDP-43 typeA

PSP

S

7

84

F

8

89

F

9

84

M

CVD

F

10 86

M

AD

F

11 88

F

S

（colocn CA） SFF

No. Age G

Dix

IC

Place of DeathF

Outside Hosp.

iNPH

F

ALS

F

21

83 M CFNS lymphoma

22

95 F

23

80 F

No. Age

G

Dix

IC

41

87

F

Early AD

S

Home

42

77

F

AD

F

TMGHIG

43

86

F

DLB＋AD

F

44

80

M

AD、DG

F

45

83

F

PSP

F

46

68

M

PSP

F

47

78

M

PSP

F

48

102

F Influenza Enc.

F

Outside

49

69

M

CVD

F

Brain Transfer

50

83

F

AD、DLB、
AGD

F

51

63

M

pending

F

52

86

M

pendingF

Nursing53

89

F

pendingF

Outside Hosp.

Outside Hosp.

54

94

M

pendingF

Nursing

Outside Hosp.

55

44

M

pendingF

Outside Hosp.

56

78

M

pendingF

Nursing

Outside Hosp.
Outside Hosp.
Outside Hosp.
Brain transfer

24

Outside Hosp.
25

78 F
74 M

PSP

F

LBD

F

Outside Hosp.

26

79 M

AD

F

Outside Hosp.

TMGHIG

27

91 F

AD

F

Outside Hosp.

TMGHIG
Outside Hosp.

28

83 F

PSP

F

90 F

AD

S

Outside Hosp.

30

87 F

AD

F

Outside Hosp.

F

PD

S

TMGHIG

31

95 M

ADG

S

13 99

F

DLB

F

Outside Hosp.

32

85 M

ADG

F

Nursing
Outside Hosp.

14 73

M

（Lung CA）

F

Outside Hosp.

33

80 F

ALS

F

15 111F

NFTD

F

Nursing

34

80 M

SMA

F

16 90

F

AD

F

Outside Hosp.

35

70 F

PSP

F

M

NFTD /
PSP/LBD/DG

36

17 97

CBD

NursingNursing

68 M

F

F

37

84 M

ALS

S

Nursing

18 72

M

CVD

F

Nursing

19 61
20 79

M
M

Encephalitis

CJD

F
F

Outside Hosp.

38 69

M

PSP

39

86 M

PDD

F
F

40

93 M

PSP

F

Outside Hosp.
Outside Hosp.
Outside Hosp.
Outside Hosp.
Outside Hosp.

Outside Hosp.

29

12 93

Nursing
Outside Hosp.

Outside Hosp.

Outside Hosp.

TMGHIG

Place of Death

Outside Hosp.

Brain Transfer
Outside Hosp.
Brain Transfer

Outside Hosp.

Preregistered donors reach 160, 56 of whom fulfilled their will.

Outside Hosp.
Outside Hosp.

September 28, 2018@
The Brain Bank for Aging Research
Tokyo Metropolitan Geriatric Hospital &Institute of Gerontology

In 2018, BBAR organized the international brain bank symposium. Professor Huitinga,
the director of Netherland Brain Bank edited Brain Bank Chapter of the Handbook ofClinical Neurology.

10The Japanese Brain Bank Network, Kansai Base
Brain Bank for Neurodevelopmental, Neurological and Psychiatric Disorders
United Graduate School of Child Development, Osaka University
Osaka University
Neurology, Psychiatry& Pathology

NHO
Osaka Toneyama& Utano (Kyoto)

Brain Donation
Fronto Temporal
Dementia
Parkinson Disease
ALS
Multiple Sclerosis
Multiple System
Atrophy
Patient Association
Parkinson disease
Multiple Sclerosis

Osaka University
Legal Medicine
Postmortem Brain
Registry of Judicial
Autopsy (Suicide)

Muscle Dystrophy
Lewy body dementia
Alzheimer Disease
Progressive Suparnucelar Palsy
Corticobasal Degeneration

Osaka Brain Bank
Promotion Foundation
PO Consortium

Osaka
Womens’andChildrens’Hospital

Neurodevelopmental
Bioresource

Japanese Version of
Suicide Bank
Autim Brain Net
Special NPO Research and
Education Support Center
CDC Research Groupto Protect the Life of
Next Generationwww.mci.gr.jp/BrainBank/

The Kansai Base, The Japanese Brain Bank Network was established in 2000 incollaboration with Osaka University, National Hospital Organization (NHO) andOsaka Prefectural Hospital Organization.

11

Japanese Brain Bank Network for Neuroscience Research
University of Tokyo, Tokushima, Kagawa, Tokyo Medical, Kitasato & Teikyo,
NCGM, NHO Tokyo, Shimoshizu, Shizuoka Epi. Neuro. & Okayama Nishi
Hosp. Yokohama Rosai. Kameda, JR Kanto, Chikamori, Tokyo Teishin

Brain Bank for Aging Res.
TMGHIG, NCGG

Brain Donation &Autopsy Consent
Tokyo Metr. Geriatr. Hosp.
& Inst. Gerontol.
Registration
Clinical, Radiological &Pathological Data

Brain Bank for Neurodevelopmental,
Neurological and Psychiatric Disorders

NCNP

Osaka Univ.
NHO Toneyama

Mihara Mem. Hosp

Open Resource for
Education and Research

Em. Prof Yasuo Ihara
a preregistrant for BBAR

Choice of Resource
Fukushimura Hosp.
Researcher

Brain Bank Committee, Jap. Soc. Neuropath.

BBNNPD and BBAR form the core of the Japanese Brain Bank Network for
Neuroscience Research, funded by MEXT, collaborating with the National Centerof Neurology and Psychiatry (NCNP), Mihara Memorial Hospital and
Fukushimura Hospital. Dr. Yasuo Ihara, a preregistered brain donor for BBAR andEmeritus Professor, the University of Tokyo, has been contributing to this framefrom the beginning.

12Japanese Brain Bank Net （JBBN)AMED Comprehensive Brain
PI: Masaki Takao

Fukushima Pre. Univ.
Brain Bank (Yabe)

Psychiatric

Nagoya Univ. Psychi.
Consortium (Iritani)

JBBN

Okayama Univ. Psych.
(Terada)Keio Univ. Psychiatr.
(Mimura)Brain Bank for Aging
Res., TMGHIG(Saito)Brain Bank for Neurod.
Neurol. Pshicitr. Dis.
Osaka U. (Murayama)

Neurological

Brain ResearchInstitute, Niigata U(Kakita)Aging Res. Inst.
Aichi Medical Univ.
(Yoshida)

AD: 1200
PD: 400
Schizo 300

Shared Data Base

Statistical advisor (Tanaka)

Academic Committee

Application

Biobank (Goto)

Matsuzawa Hosp
(Oshima)Aging and Dementiaaadd

Jpn Soc. Biol. Psychitr., Jpn Soc. Dementia Res., Jpn Soc. Neurol., JSNP, Jpn. Soc. Pathology

National Center of
Neurol.o & Psychiatr.
(Takao)IRB

Research Mnagement Center
IRB（each institute)（each institute)

Researcher

＠NCNP
Ethical advisor (Inoue)

Executive Committee
2006 Joint Ethical Guideline by JapaneseSociety of Neuropathology and JapaneseSociety of Biological Psychiatry(Evaluation and Advise)

Outside Advisory
Board（Cooperation）（Evaluation, Standardization, Qulity Control）

Late Emeritus
Professor Kanazawa
registered to BBAR.

Brain Bank Committee, JSNP

Japan Brain Bank Net (JBBN) is funded by AMED, first in 2016 and renewed in
2021. Dr. Masaki Takao, the director of NCNP Brain Bank is PI. BBAR takes
responsibility for aging and dementia and BBNNPD for suicide and pediatricregistry. The establishment of JBBN was Emeritus Professor Kanazawa’s dream,
who was registered to BBAR on January 21, 2016, just before the start of JBBN.

13

JSNP Brain Bank Committee (1986- )Chair: Murayama, S. (UO)
•
•
•
•
•
•
•
•
•
•
•
•
•

Akatsu, H. (Ger. Fukushimura H.)•Fujimura, H. （Neu.Toneyama H.) •Hasegawa, M. (Bio. Ch, TMIMR) •Ikeuchi, K. (Genome. Niigata U.) •Inoue, Y. (Ethis, IMSUT)•
Iritani, S. (Psy. Nagoya U.)•
Ito, K. (NP. Kyoto Pr. U.)•
Kakita, A. (NP. Niigata U.)•
Kato, T. (Psy, Riken)•
Izumi Y. (Neu. Tokushima U)•
Kaneda D (Fukushimura)•
Komori, T. (NP. TMNH)••
Kowa, H.（Neu. Kobe U.）

Kunii, Y. (Psy. Fukushima)
Mochizuki, H. (Neu. Osaka U.)
Tanigawa, K. (Pat. Hokkaido U.)
Nishimura, H. （Pat. Kawasaki U.)
Oshima, K. （Psy. Matsuzawa H.）
Saito, Y. (NP. TMGHIG)
Takao, M. (Lab. NCNP)
Takanashi, M.（Neu. Juntendo U.）
Tokumaru, A. (Rad. TMGHIG)
Wakabayashi, K (NP. Hirosaki U.)
Yamada, M. (NP, Shinshu U.)
Yokota, O. (Psy, Okayama U.)
Yoshida, M. (NP, Aichi M. U.)

The JSNP (Japanese Society of Neuropathology) Brain Bank Committee
supports JBBN and JBBNNR for quality assurance of neuropathologicaldiagnosis. Underlined names denote diagnostic neuropathologists for JBBN, andthose in blue denote members of JBBNNR.

14

The philosophical background• The respect for autopsy since Edo era.
• Medical positivism.
• The Brain Bank Committee, the JapaneseSociety of Neuropathology guarantees
quality assurance of brain bank from thepoints of neuropathological diagnosis,
legal regulation and COI.
• Japanese tradition,“Okagesan”.

The philosophical background of brain bank is picked up.

15

Case Study
Neuro CPC
Translational Research

Brain Bank
(Pathology Core)

Educational Core

Brain Bank
Data Base
Neuroscience Research

Clinical Core

Student, Resident,
Nurse, Patient,
Regional, Social
Genomic
Animalmodel
Cell Bank（DNA, iPS)

Molecular andProtein
Biochemical Core

Neuropsychology
Neurophysiology
Epidemiology

Image Core

MRI
PET
SPECT

The BBAR follows the framework of Alzheimer Disease Research Coordinating
Center in US.

16

Brain Bank Project
Dpt. Neurology and Psychiatry
Cognitive and Motor impairment (incl. iNPH)

Brain Bank donor
Control

Neurological and neuropsychologial examination, Neuroimages
Informed consent
CSF biomarker・apoE genotyping
Biobank (CSF, plasma and genome)

MRI

Consent of Brain Donation

FDG, amyloid and tau PETSkin biopsy for LBD

Autopsy, Registration to Brain Bank

Brain biopsy at VP shunt
Academic Committee

Research Manager & Coordinator

IRB

Researchers

From 2017, BBAR extended its research support to include biobanking of CSF,
plasma and gnome of living patients and control volunteers.

17

BBAR Resource Center• A full time coordinator.
• All BBAR records stored in our digital clinicalchart system with Brain Bank ID.
• BBAR Resource Center:24 deep freezers, including one
for a national prion back- up bank
• >7000 case paraffin blocks• BBAR Data Center: a virtual slide system foreducational output.
• BBAR Internet Conference Roomwith NCNP, OU, NHO Toneyama and Fukushimura
The Brain Bank for Aging Research (BBAR) employs a full-time and a part- time
coordinators. Our registrants’ data are all stored in clinical chart system with thebrain bank ID. We have a resource center, carrying 22 deep freezers and paraffinblocks of more than 7000 cases.
The BBAR Data Center is equipped with a virtual slide system forneuropathological education. The BBAR network conference room is connectedto the National Center for Neurology and Psychiatry (NCNP), Osaka University,
NHO Osaka Toneyama Medical Center and Fukushimura Brain Bank forneuropathological conferences once a week.

18

Autopsy of Brains• Each case is handled by anattending brain bank doctor(neuropathologist) and atechnician (specially trained), in
collaboration with an attending
general pathologist and two
technicians.
• The attending brain bank doctor
determines the frozen side.
• The doctor forms 8mm-thickserial coronal slices of the brain,
5mm- thick serial sagittal slices of
the cerebellum and 5mm- thickaxial slices of the brain stem.
• The technician takes photos andfreezes tissues immediately.
In BBAR, each autopsy is conducted by a general pathologist, an autopsy
technician and a laboratory technician, in collaboration with a neuropathologist
and a brain bank technician (2). Thus, every autopsy is handled by fiveprofessionals.

19

Sampling of Spinal Cord
Th8

Th4

C8

C4

Biceps Phrenic Nerve, Diaphragm
Th12

Sural Nerve, Short Peroneal
4% PFA 2 overnight, 2.5% GA overnight
Cauda
S2 S1 L5
EquinaDRG

Spinal cords are recovered from all cases. After sampling for histopathologicalevaluations, the remaining spinal cords are frozen for biochemical and molecularstudies.

20

Total RNA Quality Check (Dpt. Mol. Biol. Niigata
Univ. BRI)
ROW vs NP_PMI
DNA & RNA Back Up
BBAR (N=48: ROW) vs Control (N=78: NP)

RNA Quality of BBAR is better than
rapid autopsy control, probably due to avery short cooling interval (interval
between death and transfer to arefrigerator).

70
60
50
40
30
30
25
20
15
10
5
0

ROW

ROW

NP
Institute

ROW vs NP_RIN
10
9
8
7
6
5
4
3
2
1
0

Mann-Whitney’s test
P < 0.0001

ROW vs NP_28S/18S ratio

NP

2.0
1.8
1.6
1.4
1.2
1.0
0.8
0.6
0.4
0.2
0.0

ROW

NP

Institute

InstituteMann-Whitney’s test, P < 0.0001

Mann-Whitney’s test, P = 0.0002

080121 (Mon)

In collaboration with the Department of Molecular Biology, the Brain
Research Institute at Niigata University (BRIN), we check the RNA
qualities of all cases. Our cases present better quality than specimens ofa a reference institute. ApoE genotyping is determined for every case.
DNA and RNA are stored in BRIN to back up BBAR.

BBAR Resource (Frozen)• Half brain after sampling small pieces of tissues
for weak fixation.
• Entire spinal cord, after sampling the segmentsfor pathological evaluation.
• Peripheral autonomic nervous system:
sympathetic ganglia, esophago- columnar
junction, heart, skin and olfactory plate.
• Skeletal muscle: biceps brachii (for the study ofsarcopenia)• General organs: small pieces of liver, kidney,lung, esophagus• Serum (stored in the hospital laboratory).
Frozen resource includes half brain, entire spinal cord, peripheral autonomic
nervous system and skeletal muscle.

22

BBAR Protocol (www.mci.gr.jp)

Frozen Half

Fixed Half

8 areas: 4% paraformaldehyde over 2 nights(McGeer’s method @ British Columbia)
From the frozen side, eight small samples from specific anatomical areas are
fixed in 4% paraformaldehyde over two nights. The fixation simulates perfusion
followed by overnight fixation protocol that is applied to experimental animals.

23

Brain Cutting (1972.5.1-)

In collaboration of Neurology, Neuropathology, Psychiatry,
Pathology and Rehabilitation, connected via internet.
Brain Cutting is an important activity for diagnosis and education, with BBAR
and NCNP connected by internet. Emeritus Professor Kinuko Suzuki,
Department of Pathology (Neuropathology), the University of North Carolina
at Chapel Hill joins the conference after she returned to Japan.

24

BBAR Protocol: Fixed Side

③神経病理学的検索

Brain: 29 areas; Spinal Cord: 9 segments
frontal pole

frontal opeculum

CE, LDRG,
S2, L5, L2
Th12, 8, 4
C8, C4
midPons

pedunculopontine nucleus

cerebellar vermis

frontal polecerebellum with dentate
2nd frontal gy.

anterior cingulatemedobsubstantia
nigra

midbrain
Septume, accumbens
Caudate head, putamen

temporal pole

Rectal gyrus

locus ceruleus
temporal pole

Anterior commissure and Meynert

temporal pole

Copus mammilare and basal ganglia

Cerebellum with dentate

Frontaloperculum

Subthalamic nucleus, internal segment of palldum
Posterior cingulate and precuneus
Intraparietal
suclusamygdalaposterior hippocampus

Olfactory bulb
Sympathetic Ggl.
Skin

Pyryform cortex

amygdala

1st and 2 nd
temporal gyrus

Intraparietal
suclusoccipit.
pole

Splenium

Visual cortex
Thalamus and corpus callosum

Frozen Halfanterior
hippocampus

Precentral
Gyrus

posterior hippocampus

Fixed Half

Tissue sections were obtained from a fixed side, in compliance with CERAD
requirements, DLB Consensus Guideline, and Braak’s recommendation that
requires evaluation of bilateral amygdala and hippocampi.

BBAR Protocol: Histological Examination.

Internationally Standardized
Neuropathological Diagnostic Method

Paraffin block of >7,000 cases
easily accessible

Library

We have been accumulating glass slides and paraffin blocks in the BBAR
Resource Center.

26

BBAR Resource (Fixed)• 4% paraformaldehyde over two nights, one half forparaffin embedding and another half preserved in
20% sucrose PBS+0.1% NaN3
- Brain: frontal, temporal and occipital poles,
intraparietal sulcus, anterior amygdala, posterior
hippocampus, midbrain, dentate nucleus, olfactorybulb- Spinal Cord: C4/8, T4/8/12, L5, S2- Peripheral ANS: sympathetic ganglia, esophagocolumnar junction, anterior wall of the left ventricle ofthe heart, skin, olfactory plate, biceps brachii• 20% buffered formalin for 7-13 days
- Half brain, body organs
Fixed tissue resource consists of weakly stained tissues from a frozen half andformalin fixed tissues from a fixed half of the brain

27

StainingRoutine：Special：

H.E.，K.B.
Gallyas-Braak, methenamine silver,
Elastica Masson, Congo red, thioflavin S
Immunohistochemistry with automatic stainer（Ventana）
Epitope

Antibody

Clone

Aβ11-28aa
phosphorylated tau
3R/ 4R tau
phosphorylated
a- synuclein
Ubiquitin

12B2 (IBL)
AT8 (Innogene)RD3/ RD4
psyn64 (Wako)

monoclonalmonoclonalmonoclonalmonoclonal

Sigma

Phosphorylated TDP43
FUS/ TLS

PSer409/410
Sigma

polyclonalmonoclonal
polyclonal

Systematic screenings of unbiased consecutive autopsy cases are performed
with commercially available antibodies.

28

Ab

A section of hippocampus fixed in 4% paraformaldehyde presented numerous Abeta (11-28)- immune- positive deposits in the parenchyma and the walls ofvessels.

29

tau

P & CNS Screening
Y-9578Sympatheti c g ang lion
Dors al root gangli on
Spinal cord
Sacralanterior horn
Sacral posterior horn
Intermediate zone (Sacral)
Lumbar anterior horn
Lumbar pos terior horn
Lumbar anterior column
Lumbar lateral col umn
Lumbar pos terior column
Thoraci c anterior horn
Thoratic posterior horn
Intermediol ateral N. (Thoraci c)
Cervical anteri or horn
Cervical posterior horn
Medulla obl ong ata
Dors al motor N. of vagus
Hypoglossal N.
Inferior olivary N.
Pons
Pontine N.
Locus ceruleus
Subceruleus
Pedunculopontine N.
MidbrainOculomotor N.
Edinger・Westphal N.
Pars compacta of SN
Peri aqueductal gray matter
Cerebell um
Cerebel lar cortex
Cerebel lar whi te matter
Dentate N.
Interbrain / Basal gangli a
Broca's diagonal band
Hypothalamus
Nucleus basali s of Meynert
A ccumbens N.
Caudate N.
PutamenExt. globus pal lidus
Int. g lobus pall idus
Claustrum
Subthal ami c N.
Thal amus
A llocortex (Rhi nencephalon/Limbic)
Olfactory bulb periphery
A nterior olfactory N.
Piriform cortex (frontal)
Piriform cortex (temporal )A mygdala
Uncus / Ambient gyrus
Dentate gyrus
Hippocampus CA4
Hippocampus CA3
Hippocampus CA2
Hippocampus CA1
Subi cul um
Pres ubi culum
Entorhinal
Transentrhinal
Insular cortex
A nterior cingul ate gyrus
Temporal pole (medial)
Cerebral neocortex (is ocortex )Temporal pole (lateral)
T4
T2
F ronatal pole
F2
Supramargi nal gyrus
V isual association cortex
Striate area
Primary motor cortex

PT

NFT

GT

NT

NP

Lewy TDP
AG
R

L

AT
TSA
BLA

Psyn
R
L

TDP
-43

Ab
DP
R

CP
L

R

L

A/V
R
L

CCAA
R
L

0

0

0

0

0

0

0
0

0
0

0

0

0

0

0

0
0

0

0

0

0

0

0

0

0

0
0

0
0

0
0

0

0

0

0

0

0

0

0
0
0
0
0
0
0
0
0
0

0
0
0
0
0
0
0
0

0
0
0
0
0
0

0
0
0
0
0
0
0
0

0
1

0
1

0
0

0
1

0
0

0
0

0
0

0
0

0
0

0
0

0

0

0

0

0
0

0
0
0
0
0

0

We screen all cases immunohistochemically. Blue highlights denote theperipheral autonomic nervous system, and the orange rectangle, the spinal cord.

30

BBAR Degenerative Pathology Database
BBAR

Y96XX

A/G

CDR

PMI

NFT

AT8

SP

CERAD

Thal

LB

LB score

DLB 3rd

93M

3

11:22

4/3

3/3

2

2

5

4

4

Limbic(amygdala

Grain

AA

AT

UD

TDP

ApoE

RIN

NPD

0.5/
0.5

1C

1

3

T1M1S03/3

8.1

AD, LBD,
CVDE

predominant)A/G age/ gender
CDR (clinical dementia rating):
0-3
PMI: postmortem interval
NFT (tangle: Braak Stage):
0-6
AT8 (tangle: AT8 Stage)
0-6
SP (senile plaque: Braak Stage):
0-3
CERAD
0-3 (0- C)
Thal (amyloid Thal Stage)
0-5
Lewy (Lewy body, BBAR Stage):
0-5
DLB score (DLB 1st Consensus Guideline)
DLB 3rd (DLB 3rd Consensus Guideline)
Grain (argyrophilic grain, Saito Stage):
0-3
AA (amyloid angiopathy, BBAR Stage):
0-3
AT (astrocytic tangle):
0-3
UD (ubiquitinated dots):
0-3
TDP (TDP-43 proteinopathy, temporal, medulla and spinal) 0-3
ApoE (apoE genotyping)
RIN (RNA intergrity number)
NPD: neuropathologic diagnosis (AD: Alzheimer disease; LBD: Lewy body disease; CVDE: embolic infarct)

Each case is evaluated using international standards. Researchers who apply to
BBAR choose samples based on this database.

31Braak
NFT/ SPDNA Resource (1,890 cases)

0

0
34

I
314

II
102

III
46

IV
12

V
1

VI
0

計
509

66.3

75.8

81.8

85.6

85.4

81.0

-

77.5

A

16

350

149

74

23

1

0

613

75.5

78.0

83.6

86.2

88.6

99.0

-

80.6

8

169

91

70

23

2

1

364

76.1

79.9

82.8

85.6

91.2

82.0

94.0

82.4

3

50

51

80

80

100

40

404

76.0

79.4

83.0

84.5

86.6

86.4

83.9

84.4

61

883

393

270

138

104

41

1890

70.5

77.7

82.9

85.4

87.6

86.4

84.1

80.9

B
C
計

Case #
Average Age

Alzheimer Disease: 220/ 1890 = 11.6%

DNA resources represent progressive accumulation of tangles and plaques. We
adopt Braak NFT Stage equal to or more than IV and SP Stage C for diagnosis of
Alzheimer disease or Alzheimer dementia in 2011 NIA- AA classification.

32

Symposium 12
Renpei Sengoku

AD Change

Peripheral
autonomic
nervous system

Brain
stem

SC

Olfactory

CerebralCortex75 Lewy+/
205(36.6%)

PD/ DLB

In our most recent 205 consecutive autopsy cases, 36% contained Lewy bodypathology. In 2014- 2016 we received funding from the Michael J Fox
Association as a Lewy body disease body bank.

33

Higashihara 47 ALS/ MND Brain and Spinal Cord ResourceM.
(with 300 frozen control spinal cord)

Matsubara, ALS/MND Sym
T.
@Perth 2019

Westmead detecting upper motor neuron sigh for early diagnosis of ALS

徳島大学、ビハーラ花の里病院剖検を広島西医療センターで行う体制の元、筋萎縮性側索硬化症脳・脊髄バンクを高齢者ブレインバンクに構築しています。健康長寿医療センター脳神経内科東原医長は2年間豪シドニーWestmead研究所で上位運動ニューロンの二発磁気刺激による神経生理検査法を取得し、帰国後前頭側頭型認知症・筋萎
縮性側索硬化症（ALS）クリニックを立ち上げました。豪は医療費ゼロシーリングで、病理解剖が制限されており、剖検による確認を、Westmeadとの共同研究として開始予定です。

34

The first autopsy case of JADNI participant from Tohoku
University, just after the Great East Japan Earthquake

I will go anywhere when there is a will of brain donation

This is the first JADNI participant autopsy from Tohoku University. The autopsy
was done just after the Higashinippon Earthquake, and I went to Tohoku
University to recover this brain.

35

CJD Surveillance Commitee
Pathology Core
• To promote autopsies of prion disease.
• To receive autopsies of outside cases.
• To report to the committee on autopsy- provenprion cases (pathology route)• Quality control of pathological findings ofregistered cases.
• To establish a national prion back- up bank.
• To study natural course of prion disease.
Grants in Aid from Ministry of Health, Labor and Welfare, Japan
BBAR is the pathology core of the Japanese CJD Surveillance Committee andcontribute to prion research.

36

International Collaboration• MOU with Seoul University (Prof. Park) for
Korean Brain Bank
• MOU with National Neuroscience Institute ofSingapore for Neuronal Intranuclear Inclusion
Body Disease• Collaboration with Sydney Parkinson Disease
Brain Bank funded by Michael J Fox
Foundation (Prof. Halliday).
• Collaboration with Sydeney Westmead
Hospital for ALS research

BBAR promotes international collaboration.

37

Brain Bank and Bioresource Center, Osaka University (2021)
Brain Bank for Neurodevelopmental, Neurological and Psychiatric Disorder
Chair (Prof.)
Concurrent (Neuro)
M.D. Ph.D. Course

Murayama, S.
Concurrent
Assi. P. Beck, G.
Yonenobu, Y.
Yamashita, R.

Prof. Mochizuki, H. (Neurology)
Prof. Taniike, M. (Child Develop.)
Prof. Ikeda M. (Psychiatry)Prof. Matsumoto, H. (Legal Med.)BBAR Project (2021)
Brain Bank for Aging Research
Chair
Saito, Y.
Pathology Core
Murayama, S.
Clinical Core
Iwata, A.
Staff
Matsubara, H.
Fellow
Arakawa, A.
Resident
Orita, M
Visiting Scholar
Uchino, A.
Shioya A
Technician
Harada, M.
Research Manager
Morishima, M.
Coordinator
Obata, M.
Neuropathology
Chair
Saito, Y.
Staff (cross appoint)
Murayama, S.
Chair

PET Center
Ishii, K.

Neurology
Iwata, A.
Kanemaru, K.
Nishina, N.
Higashihara, M.
Ihara, R.
Staff:
Hatano A
Res. Resident:
Morimoto, S.
Resident
Kimura, T.
Rehabilitation
Senior:Kato, T.
Psychiatry
Chair:
Furuta, K.
Pathology
Chair
Arai, T.
Chair:
Co- Chair:Vice- Chair,

Chair

Radiology
Tokumaru, A.

The list of BBNNPD and BBAR members.

38