Tau positron emission tomographic imaging in aging and early Alzheimer disease.
OBJECTIVE
Detection of focal brain tau deposition during life could greatly facilitate accurate diagnosis of Alzheimer disease (AD), staging and monitoring of disease progression, and development of disease-modifying therapies.


METHODS
We acquired tau positron emission tomography (PET) using (18)F T807 (AV1451), and amyloid-β PET using (11)C Pittsburgh compound B (PiB) in older clinically normal individuals, and symptomatic patients with mild cognitive impairment or mild AD dementia.


RESULTS
We found abnormally high cortical (18)F T807 binding in patients with mild cognitive impairment and AD dementia compared to clinically normal controls. Consistent with the neuropathology literature, the presence of elevated neocortical (18)F T807 binding particularly in the inferior temporal gyrus was associated with clinical impairment. The association of cognitive impairment was stronger with inferior temporal (18)F T807 than with mean cortical (11)C PIB. Regional (18)F T807 was correlated with mean cortical (11)C PiB among both impaired and control subjects.


CONCLUSIONS
These findings suggest that (18)F T807 PET could have value as a biomarker that reflects both the progression of AD tauopathy and the emergence of clinical impairment.
Division of Nuclear Medicine and Molecular Imaging, Boston, MA.|Department of Neurology, Boston, MA.|Department of Radiology, Massachusetts General Hospital, Boston, MA.|Center for Alzheimer Research and Treatment, Department of Neurology, Brigham and Women's Hospital, Boston, MA.|Harvard Medical School, Boston, MA.
Keith A
KA
Johnson
Division of Nuclear Medicine and Molecular Imaging, Boston, MA.|Center for Alzheimer Research and Treatment, Department of Neurology, Brigham and Women's Hospital, Boston, MA.|Athinoula A. Martinos Center for Biomedical Imaging, Boston, MA.
Aaron
A
Schultz
Department of Medicine (Biostatistics Center), Massachusetts General Hospital, Boston, MA.|Harvard School of Public Health, Boston, MA.
Rebecca A
RA
Betensky
Division of Nuclear Medicine and Molecular Imaging, Boston, MA.|Department of Radiology, Massachusetts General Hospital, Boston, MA.
J Alex
JA
Becker
Division of Nuclear Medicine and Molecular Imaging, Boston, MA.|Department of Radiology, Massachusetts General Hospital, Boston, MA.|Harvard Medical School, Boston, MA.|Athinoula A. Martinos Center for Biomedical Imaging, Boston, MA.
Jorge
J
Sepulcre
Department of Neurology, Boston, MA.|Center for Alzheimer Research and Treatment, Department of Neurology, Brigham and Women's Hospital, Boston, MA.|Harvard Medical School, Boston, MA.
Dorene
D
Rentz
Department of Neurology, Boston, MA.|Center for Alzheimer Research and Treatment, Department of Neurology, Brigham and Women's Hospital, Boston, MA.
Elizabeth
E
Mormino
Department of Neurology, Boston, MA.|Center for Alzheimer Research and Treatment, Department of Neurology, Brigham and Women's Hospital, Boston, MA.|Harvard Medical School, Boston, MA.
Jasmeer
J
Chhatwal
Department of Neurology, Boston, MA.|Center for Alzheimer Research and Treatment, Department of Neurology, Brigham and Women's Hospital, Boston, MA.|Harvard Medical School, Boston, MA.
Rebecca
R
Amariglio
Department of Neurology, Boston, MA.|Center for Alzheimer Research and Treatment, Department of Neurology, Brigham and Women's Hospital, Boston, MA.|Harvard Medical School, Boston, MA.
Kate
K
Papp
Department of Neurology, Boston, MA.|Center for Alzheimer Research and Treatment, Department of Neurology, Brigham and Women's Hospital, Boston, MA.|Harvard Medical School, Boston, MA.
Gad
G
Marshall
Department of Neurology, Boston, MA.|Harvard Medical School, Boston, MA.
Mark
M
Albers
Division of Nuclear Medicine and Molecular Imaging, Boston, MA.|Department of Radiology, Massachusetts General Hospital, Boston, MA.
Samantha
S
Mauro
Division of Nuclear Medicine and Molecular Imaging, Boston, MA.|Department of Radiology, Massachusetts General Hospital, Boston, MA.
Lesley
L
Pepin
Division of Nuclear Medicine and Molecular Imaging, Boston, MA.|Department of Radiology, Massachusetts General Hospital, Boston, MA.
Jonathan
J
Alverio
Division of Nuclear Medicine and Molecular Imaging, Boston, MA.|Department of Radiology, Massachusetts General Hospital, Boston, MA.
Kelly
K
Judge
Division of Nuclear Medicine and Molecular Imaging, Boston, MA.|Department of Radiology, Massachusetts General Hospital, Boston, MA.
Marlie
M
Philiossaint
Division of Nuclear Medicine and Molecular Imaging, Boston, MA.|Department of Radiology, Massachusetts General Hospital, Boston, MA.
Timothy
T
Shoup
Division of Nuclear Medicine and Molecular Imaging, Boston, MA.|Department of Radiology, Massachusetts General Hospital, Boston, MA.|Harvard Medical School, Boston, MA.
Daniel
D
Yokell
Division of Nuclear Medicine and Molecular Imaging, Boston, MA.|Department of Neurology, Boston, MA.|Harvard Medical School, Boston, MA.|Athinoula A. Martinos Center for Biomedical Imaging, Boston, MA.
Bradford
B
Dickerson
Department of Neurology, Boston, MA.|Harvard Medical School, Boston, MA.
Teresa
T
Gomez-Isla
Department of Neurology, Boston, MA.|Harvard Medical School, Boston, MA.
Bradley
B
Hyman
Division of Nuclear Medicine and Molecular Imaging, Boston, MA.|Department of Radiology, Massachusetts General Hospital, Boston, MA.|Harvard Medical School, Boston, MA.
Neil
N
Vasdev
Department of Neurology, Boston, MA.|Center for Alzheimer Research and Treatment, Department of Neurology, Brigham and Women's Hospital, Boston, MA.|Harvard Medical School, Boston, MA.|Athinoula A. Martinos Center for Biomedical Imaging, Boston, MA.
Reisa
R
Sperling
D000368:Aged; D000369:Aged, 80 and over; D000375:Aging / Q000378:metabolism*; D000544:Alzheimer Disease / Q000378:metabolism* / Q000503:physiopathology; D016229:Amyloid beta-Peptides / Q000378:metabolism; D000814:Aniline Compounds; D015415:Biomarkers / Q000378:metabolism; D002243:Carbolines / Q000378:metabolism*; D002540:Cerebral Cortex / Q000378:metabolism*; D060825:Cognitive Dysfunction / Q000378:metabolism* / Q000503:physiopathology; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D049268:Positron-Emission Tomography / Q000379:methods*; D013702:Temporal Lobe / Q000378:metabolism; D013844:Thiazoles; D016875:tau Proteins / Q000378:metabolism*
C475519:2-(4'-(methylamino)phenyl)-6-hydroxybenzothiazole; D016229:Amyloid beta-Peptides; D000814:Aniline Compounds; D015415:Biomarkers; D002243:Carbolines; D013844:Thiazoles; D016875:tau Proteins; C000591008:7-(6-fluoropyridin-3-yl)-5H-pyrido(4,3-b)indole