AOCNP＠India, 2021

Japan Brain Bank Network
Specially Appointed Professor,
Brain Bank for Neurodevelopmental, Neurological andPsychiatric Disorders,
United Graduate School of Child Development,
Osaka University
Specially Appointed Researcher
The Brain Bank for Aging Research
Tokyo Metropolitan Geriatric Hospital and Institute ofGerontology (Cross Appointment)

Shigeo Murayama M.D. Ph.D.
I will talk about Japan Brain Bank Network. I am working with two brain banksystem in Japan.

1

My Background• I am a Zen master 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 is a buddhist priest and feels sincere respect for people in India.

2

COI
Honorable Member: the Japanese Societies of Neurology,
Neuropathology and Dementia Research
Associate Editor, Journal of Neuropathology andExperimental Neurology
Visiting Professor: Tokushima, Hiroshima, Tokyo Medical,
Doshisha and Osaka City Universities;
Neuropathology Consultant: National Center for Global
Medicine, National Hospital Organization, Tokyo,
Shimoshizu, Shizuoka Epilepsy and Neurology, West
Hiroshima and Okinawa Hospitals; Kagawa University;
Kameda, Yokohama Rosai, Toranomon, NTT East Kanto
and Chikamori Hospitals

My COI is as follows. I will go anywhere to fulfill the will of brain donation.

3

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 defined as activity of TMGHIG funded by
Tokyo Metropolitan government in collaboration of all members of our institute.

4

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.

5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/Japanese Brain Bank Network, Kansai Base was established in 2020 incollaboration with Osaka University, National Hospital Organization (NHO) andOsaka Prefectural Hospital Organization.

6

Donor Card

Dr. Toyokura, the Late Emeritus Professor the University of Tokyo and Emeritus
President of TMGHIG was the founder of our brain donation program.
“Please use my body to cure the incurable diseases that will kill me.” He sufferedfrom cardiomyopathy with a mutation of myosin light chain and died at age of 80
years.

7

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.

8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.

9

The Brain Bank Network
Institute
Clinician/ Pathologist
BBAR
Iwata, A./ Saito, Y.
NCNP
Takahashi, Y./ Takao, M.
MiharaMihara, B./ Takao, M.
Fukushimura
Kaneda, D./ Hashizume, Y.
Osaka Univ.
Mochizuki, H./ Murayama, S.
NHO Toneyama
Inoue, K.
Tokushima, U.
Izumi, Y./ Tsuneyama, K.
Univ. Tokyo
Kubota, A./ Ikemura, M.
NCGM
Arai, T./ Igari, T.
NHO Tokyo
Komiya, T./
NHO Shizuoka
Obi, T.
Yokohama Rosai
Imafuku, I/ Kakuta, Y.
KamedaAndo, T/ Takeuchi, R.
Kitazato Y.
Nishiyama, K./ Ichinohe, M.
Mita IUHW
Iwata, N./ Aida, S.
Kagawa U.
Kamada, M./ Ueno, M.
Toranomon
Uesaka, Y./ Ito, S.
Teikyo, U.
Sonoo, M./ Uozaki, H.
Tokyo Teishin
Shiio, Y./ Kishida, Y.
Tokyo Medical U. Aizawa, H./ Kuroda, M.
NHO E. Hiroshima Watanabe, C./Tachiyama, Y
Osaka City Univ. Ito, Y./ Osawa, M.
NHO Sagamihara Hasegawa, I./ Yagishita, S.
NHO Okinawa
Suwazono, S./ Atami, E.
Open Resource
Inst. Collection （MEXT、AMED)2012 2013 2014 2015 2016 2017 2018 2019 2020
63
39 39 45
64 52
39
36
36
10
10 11
9
13 18
24
14
22
29
26 15 19
23
16 19
33
18
36
31
27 25
25
21 25 33
40
3
4
6
6
5
18 16
12
1
3
5 10
4
12
4
5
3
28
23 22 25
26 15
17
18
21
23
16 17 27
17
17
9
9
7
5
5
2
4
3
0
1
1
1
1
2
2
4
6
6
4
2
2
1
6
6
8
8
4
4
4
2
12
10
6
9
12
10(2) 10(2) 10(2) 5(4)
7
9
5
4
2
6
6
1
1
2
3
2
0
2
1
1
2
0
2
4
3
1
1
1
2
1
0
3
1
2
2
3
1
8
2
3
2
2
0
4
0
4
2
0
5
2
2
3
5
3
0
3 3(2)
1
0
0
1
0
1
3
4
4
2
4
0
1
1
1
1
0
1
0
8 10
18 18
17
8
1
2
2
4
2
0
140 109 100 110 156 155 168 171 163
7985
84 105 74
69 50
67 35

We tried to increase open brain resource for neuroscience research, incollaboration with clinicians and pathologists.

10Brain Bank Registrants BBAR (Aug. 2021) : (Preregistrants: 203）
Con. Place of death/ auto.

No. 年齢

性別

Dix

同意

28

83

F

PSP

F

Body transfer

Body transfer

29

90

F

AD

S

F

Brain transfer

30

87

F

AD

CBD-PNFA/
TDP-43 type A

F

Body transfer

31

95

M

F

AD

F

Brain transfer

32

85

M

91

M

AD/CAA/DG/
HS-TDP-43

S

Body transfer

33

80

84

F

PSP

S

Body Transfer

34

80

89

F

(Colon Ca)S

TMGHIG

35

70
68

No. Age Gen.

Dix

1

80

M

Heart

S

TMGHIG

2

83

M

FAD

F

3

79

F

FAD

4

69

F

5

86

6
7
8

死亡場所・剖検施設 No. 年齢

性別

Dix

同意

死亡場所・剖検施設

55

44

M

SPG11

F

Body transfer

Body transfer

56

78

F

AGD

F

Body transfer

F

Body transfer

57

85

M

CJD MV1S

Body transfer

AGD

S

Body transfer

58

85

M

S

Body transfer

AGD

F

Body transfer（renal
Ca）

59

61

M

ALS

S

Brain transfer

F

ALS

F

Body transfer

60

SMA

86

M

Body transfer

F

Body transfer

（Lung
Ca）

F

M
F

PSP

F

Body transfer

61

82

F

（CVD）

F

TMGHIGM

CBD

F

Body transfer

62

85

F

PSP

F

Body transfer

63

92

M

AD

F

Body transfer

64

61

F

fCJD

F

Body transfer

65

85

F

CJD/PDF

Body transfer

66

82

F

PSP

F

Body transfer

67

49

F

NMO

F

Body transfer

68

82

F

PSP

F

Body transfer

69

72

M

AD

F

Body transfer

70

41

F

SCA1

F

Body transfer

71

83

M

AD

F

Body transfer

72

92

M

AD

F

Body transfer

73

91

F

AD

F

TMGHIG

74

63

F

Tauopathy

F

Body transfer

75

85

M

SCA6

S

Body transfer

76

82

M

AD

S

Body transfer

77

57

M

CJD

F

Body transfer

78

86

M

Y-10227(pending)

F

Body transfer

79

65

F

Y-10231(pending)

F

Body transfer

9

84

M

CVD

F

TMGHIG

36

10

86

M

AD

F

TMGHIG

37

84

M

ALS

S

Body transfer

11

88

F

DLB

F

Body transfer

38

69

M

PSP

S

Brain transfer

12

93

F

PD

S

TMGHIG

39

86

M

PDD

F

Body transfer

Body transfer

40

93

M

PSP

F

Brain transfer

87

F

Early ADS

Body transfer

13

99

F

DLB

F

14

73

M

（肺癌）

F

Body transfer

41

15

111

F

NFTD

F

Body transfer

42

77

F

AD

F

Body transfer

Body transfer

43

86

M

DLB/ADF

Body transfer

44

80

M

AD/AGDF

Body transfer

45

83

F

PSP

F

Body transfer

46

68

M

PSP

F

Body transfer

47

78

M

PSP

F

Body transfer

48

102

F

(Influ.)F

Body transfer

49

69

M

CVD

F

Brain trasfer

50

83

F

AD/DLBF

Body transfer

51

63

M

Cereb. Con.

F

Body transfer

16

90

F

AD

F

Body transfer

F

17

97

M

NFTD/
PSP/LBD/DG

18

72

M

CVD

F

Body transfer

19

61

M

Encephalit.

F

Body transfer

20

79

M

CJD

F

Body transfer

21

83

M

Malignant ly.

FBody transfer

22

95

F

iNPH

F

Body transfer

23

80

F

ALS

F

TMGHIG

24

78

F

PSP

F

Body transfer

25

74

M

LBD

F

Body transfer

52

86

M

FTLD-TDP
typeC

F

Body transfer

89

F

CJD

F

Body transfer

94

M

eAD/AGDF

Body transfer

26

79

M

AD

F

Body transfer

53

27

91

F

AD

F

Body transfer

54

Brain Bank Registrants in BBAR reached 79 among 203 preregistrants.

2020 Collaboration
PI

Institutewww.mci.gr.jp/BrainBank/

Research theme

1 Ikeuchi, K.

NIBR

2 Kuwano, R.

NIBRm iRNA 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

Immunocytochem istry of ALS

9 Yamanaka, K.

Enviro. Res . Nagoya Univ.

Novel biomarker in neurodegeneration

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. Doshis ha Univ.

Imaging m ass spectroscopy of hum an brain

13 Tanaka, M.

Riken

DISC1 and neurodegeneration

14 Tsuji, S.

Neurol. UTGenomic screening in neurodegeneration

15 Ishikawa, K.

Neurol. TMDU

Genomic screening of ACA

16 Iwata, A.

Neurol. UT

Epigenetics of ALS

17 Tokumaru, A.

Raidiol. TMGHIG

W hite matter change in MRI

18 Hattori, N.

Neurol. Junten. Univ.

Genomic screening of PD

19 Kwak, S.

Neurol. UTRNA editing in ALS

20 Kubo, S.

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.

Fukushim a Med. Univ.

26 Sengoku, R.

Neurol. TMGHIG

Pathology of olfactory plate

27 Hashimoto, K.

Psy. Res. Cntr. Chiba Univ.

Lipid metabolism in PD

Life Sci. Doshis ha Univ.

anti- oxidant DJ1 in LBD

28 Saito, Y.

Glycosylation in AD

29 Kato, T.

Riken

Neuropathology of depres sion

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

34 Ishii, K.

Pet Center TMGHIG

Neuropathology of tau imaging

35 Im aizumi, K.

Hiroshim a Univ.

ER stress

36 Nagai, Y.

Osaka Univ.

exome analysis of in vivo proteostas is

37 Araki, I.

NCNP

BACE1 and synapse degeneration in AD

38 Yamagoshi, T.

NCGG

Salivary gland in aging

Chaperone- mediated autophagy

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 dementia

42 Ishiura, H.

Neurol. UTHigh grade genome study of neurodegeneration

BBAR provided its resource to 42 laboratories in 2020.

12

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.

13

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.

14

JSNP Brain Bank Committee (1986- )
•
•
•
•
•
•
•
•
•
•
•
•
•
•
•

Chair: Murayama, S. (UO)
Adachi, T. (Tottori U.)• Tanigawa, K. (Pat. Hokkaido U.)
Ikeuchi, K. (Genome. Niigata U.) • Taniguchi, D.（Neu. Juntendo U.）
Izumi Y. (Neu. Tokushima U)• Tokumaru, A. (Rad. TMGHIG)
Ito, K. (NP. Kyoto Pr. U.)• Nishida, N. (For. Toyama U.)
Inoue, Y. (Ethis, IMSUT)• Nishimura, H. （Pat. Kawasaki U.)
Iritani, S. (Psy. Nagoya U.)• Hasegawa, M. (Bio. Ch, TMIMR)
Oshima, K. （Psy. Matsuzawa H.） • Fujimura, H. （Toneyama H.)
Kato, T. (Psy, Riken)• Furuta T (Pat. Saga U.)
Kaneda, D. (Fukushimura H.)• Matsumoto, H. (For. Osaka U.)
Kunii, Y. (Psy. Fukushima)• Beck, G. (Neu. Osaka U.)
Komori, T. (NP. TMNH)• Miki, Y (NP. Hirosaki U.)
Kowa, H.（Neu. Kobe U.）• Yamada, M. (NP, Shinshu U.)
Saito, Y. (NP. TMGHIG)• Yokota, O. (Psy, Okayama U.)
Shimizu, H. (NP. Niigata U.)• Yoshida, M. (NP, Aichi M. U.)
Takao, M. (Lab. NCNP)The JSNP (Japanese Society of Neuropathology) Brain Bank Committee
supports JBBN and JBBNNR for quality assurance of neuropathologicaldiagnosis. The committee covers all areas of Japan.

15

The philosophical background• The respect for general autopsy since Edo
era for evidence- based medicine.
• The Brain Bank Committee, the JapaneseSociety of Neuropathology supports quality
assurance of brain banking inneuropathological diagnosis, legal
regulation and COI.
• Japanese tradition,“Okagesan”.

The philosophical background of brain bank is deep respect for autopsy. The
brain bank committee supports brain banking for more than twenty years.
Japanese tradition, “Okagesan” is based on this activity.

16

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.

17

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

Our brain bank projet includes biobanking of CSF, plasma and gnome of living
patients and controls.

18

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, Osaka U., Toneyama and Fukushimura
The Brain Bank for Aging Research (BBAR) employs a full-time coordinators. All
BBAR registrants’ data are stored in clinical chart system with the brain bank ID.
We have a resource center, carrying 24 deep freezers and paraffin blocks ofmore 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 forneuropathology quality assuarance conference once a week.

19

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 our brain bank system, each autopsy is conducted by a general pathologist, an
autopsy technician and a laboratory technician, in collaboration with aneuropathologist and a brain bank technician (2). Thus, every autopsy is handled
by at least five professionals.

20

Spinal Cord Banks
C4

Phrenic Nerve
Diaphragm

C8

Th4

Th8

BicepsTh12

L5 S1 S2

Cauda
EquinaDRG

Sural Nerve Short Peroneal

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

21

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 to meet NIH requirement. Niigata works as DNA/RNA backup bank.

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, skeletal muscle, small pieces of general organs and serum.

23

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 for better correlation with studies ofexperimental animals.

24

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, connectedwith BBAR, NCNP, Osaka University and Toneyama Medical Center.

25

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
2 nd 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

1 st and 2 nd
temporal gyrus

anterior
hippocampus
Splenium

Precentral
Gyrus

Intraparietal
suclusoccipit.
pole

Visual cortex
Thalamus and corpus callosum

Frozen Half

posterior hippocampus

Fixed Half

Tissue blocks 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.

27

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 paraform- fixed tissues from a frozen half andbuffered- formalin fixed tissues from a fixed half of the brain

28

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 (Fujirebio)
RD3/ RD4
psyn64 (Wako)

monoclonalmonoclonalmonoclonalmonoclonal

Sigma

Phosphorylated TDP43
FUS/ TLS

PSer409/410
Sigma

polyclonalmonoclonal
polyclonal

Immunohistochemical screenings of all autopsy cases are performed withcommercially available antibodies.

29

Ab

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

30

tau

P & CNS Screening
Y-9578Sympathetic gangli on
Dorsal root g angl ion
Spi nal cord
Sacral anteri or horn
Sacral pos teri or horn
Intermediate zone (Sacral )Lumbar anterior horn
Lumbar pos teri or horn
Lumbar anterior column
Lumbar l ateral column
Lumbar pos teri or col umn
Thoracic anteri or horn
Thoratic posteri or horn
Intermediol ateral N. (Thoracic)
Cervi cal anterior horn
Cervi cal posteri or horn
Medul la obl ong ata
Dorsal motor N. of vagus
Hypogl os sal N.
Inferior olivary N.
Pons
Pontine N.
Locus ceruleus
Subcerul eus
Pedunculoponti ne N.
Midbrai n
Ocul omotor N.
Edi nger・Westphal N.
Pars compacta of SN
Periaqueductal gray matter
Cerebell um
Cerebell ar cortex
Cerebell ar white matter
Dentate N.
Interbrain / Basal g angl ia
Broca's di ag onal band
Hypothalamus
Nucl eus bas al is of Meynert
Accumbens N.
Caudate N.
Putamen
Ex t. g lobus palli dus
Int. g lobus pal li dus
Claus trum
Subthalami c N.
Thal amus
All ocortex (Rhi nencephal on/Limbic)
Olfactory bulb periphery
Anterior olfactory N.
Piriform cortex (frontal)
Piriform cortex (temporal )Amyg dal a
Uncus / Ambi ent gyrus
Dentate g yrus
Hippocampus CA4
Hippocampus CA3
Hippocampus CA2
Hippocampus CA1
Subi cul um
Presubiculum
Entorhinal
Trans entrhi nal
Insular cortex
Anterior cingulate g yrus
Temporal pole (medial)
Cerebral neocortex (is ocortex )Temporal pole (lateral)
T4
T2
Fronatal pole
F2
Supramarg inal gyrus
Vis ual ass oci ation cortex
Striate area
Pri mary 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.

31

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 with international standards. Researchers who apply to
BBAR choose samples based on this database.

32

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.

33

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. We published the results in Acta Neuropathologica in 2020.

34

ALS/MND Sym@Perth 2019
Westmead detecting upper motor neuron sigh for early diagnosis of ALS

Higashihara 54 ALS/ MND Brain and Spinal Cord Resource Matsubara,, T.
M.
(300 frozen control spinal cord) in 506 JaCALS registrants

We establish ALS bank in collaboration with Tokushima University together with
300 control spinal cord.

35

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

I recovered 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.

36

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, JapanI am a pathology core of the Japanese CJD Surveillance Committee andcontribute to prion research.

37International Collaboration• Collaboration with Sydney Parkinson Disease
Brain Bank funded by Michael J Fox
Foundation (Prof. Halliday).
• Collaboration with Sydeney Westmead
Hospital for ALS research• Collaboration with Cambridge for atomic force
microscope

We promote international collaboration.

38

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 (BBAR)
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
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.
Kuriyama,
Res. Resident:
Morimoto, S.
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.

39