Imaging of tau pathology in a tauopathy mouse model and in Alzheimer patients compared to normal controls.
Accumulation of intracellular tau fibrils has been the focus of research on the mechanisms of neurodegeneration in Alzheimer's disease (AD) and related tauopathies. Here, we have developed a class of tau ligands, phenyl/pyridinyl-butadienyl-benzothiazoles/benzothiazoliums (PBBs), for visualizing diverse tau inclusions in brains of living patients with AD or non-AD tauopathies and animal models of these disorders. In vivo optical and positron emission tomographic (PET) imaging of a transgenic mouse model demonstrated sensitive detection of tau inclusions by PBBs. A pyridinated PBB, [(11)C]PBB3, was next applied in a clinical PET study, and its robust signal in the AD hippocampus wherein tau pathology is enriched contrasted strikingly with that of a senile plaque radioligand, [(11)C]Pittsburgh Compound-B ([(11)C]PIB). [(11)C]PBB3-PET data were also consistent with the spreading of tau pathology with AD progression. Furthermore, increased [(11)C]PBB3 signals were found in a corticobasal syndrome patient negative for [(11)C]PIB-PET.
Molecular Imaging Center, National Institute of Radiological Sciences, 4-9-1 Anagawa, Inage-ku, Chiba, Chiba 263-8555, Japan.
Masahiro
M
Maruyama
Hitoshi
H
Shimada
Tetsuya
T
Suhara
Hitoshi
H
Shinotoh
Bin
B
Ji
Jun
J
Maeda
Ming-Rong
MR
Zhang
John Q
JQ
Trojanowski
Virginia M-Y
VM
Lee
Maiko
M
Ono
Kazuto
K
Masamoto
Harumasa
H
Takano
Naruhiko
N
Sahara
Nobuhisa
N
Iwata
Nobuyuki
N
Okamura
Shozo
S
Furumoto
Yukitsuka
Y
Kudo
Qing
Q
Chang
Takaomi C
TC
Saido
Akihiko
A
Takashima
Jada
J
Lewis
Ming-Kuei
MK
Jang
Ichio
I
Aoki
Hiroshi
H
Ito
Makoto
M
Higuchi
D000367:Age Factors; D000368:Aged; D000544:Alzheimer Disease / Q000000981:diagnostic imaging / Q000473:pathology*; D000631:Aminopyridines / Q000493:pharmacokinetics; D016229:Amyloid beta-Peptides / Q000378:metabolism; D000814:Aniline Compounds; D000818:Animals; D001345:Autoradiography; D052160:Benzothiazoles / Q000737:chemistry / Q000493:pharmacokinetics; D001921:Brain / Q000000981:diagnostic imaging / Q000187:drug effects / Q000473:pathology*; D001931:Brain Mapping; D002135:Calcium-Binding Proteins; D002247:Carbon Isotopes / Q000493:pharmacokinetics; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D008840:Microfilament Proteins; D008875:Middle Aged; D009154:Mutation / Q000235:genetics; D049268:Positron-Emission Tomography; D017433:Protein Structure, Secondary; D024801:Tauopathies / Q000000981:diagnostic imaging / Q000473:pathology*; D013844:Thiazoles; D016875:tau Proteins / Q000235:genetics / Q000378:metabolism*
C475519:2-(4'-(methylamino)phenyl)-6-hydroxybenzothiazole; C539976:2-(6-(methylamino)pyridin-3-yl)-1,3-benzothiazol-6-ol; C112986:AIF1 protein, human; D000631:Aminopyridines; D016229:Amyloid beta-Peptides; D000814:Aniline Compounds; D052160:Benzothiazoles; D002135:Calcium-Binding Proteins; D002247:Carbon Isotopes; D004268:DNA-Binding Proteins; D008840:Microfilament Proteins; D013844:Thiazoles; D016875:tau Proteins; C058836:benzothiazoline