Tau positron emission tomographic imaging in aging and early A lzheimer disease
Open accessAbstract
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. INTERPRETATION: 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.
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Elevated tau PET binding in medial temporal lobe structures and neocortex is strongly associated with positive amyloid PET scans and with clinical impairment across the normal aging to dementia clinical spectrum.
“Elevated tau PET binding in both medial temporal lobe structures and the neocortex is strongly associated with positive amyloid PET scans and with clinical impairment across the normal aging to dementia clinical spectrum [82,130–141].”
From NIA‐AA Research Framework: Toward a biological definition of Alzheimer's disease (2018) · cites this paper as [131]
Results §4 (page unavailable) links inferior temporal tau PET binding to greater clinical impairment and higher amyloid PET retention, including across the full sample. Results §2 reports medial temporal binding in some clinically normal subjects, while the Discussion says hippocampal binding did not consistently increase with more advanced disease. The paper therefore supports the neocortical association but not the claim that binding in medial temporal structures is likewise strongly associated with both amyloid positivity and clinical impairment. (LLM, conf=0.86)
Experimental — accuracy not yet measuredThe cross-sectional association between regional tau PET and global Aβ PET is well-characterized.
“we examined the influence of sex to modify the well-characterized cross-sectional association between regional tau PET and global Aβ PET.14–16”
From Sex Differences in the Association of Global Amyloid and Regional Tau Deposition Measured by Positron Emission Tomography in Clinically Normal Older Adults (2019) · cites this paper as [14]
These results are consistent with previously observed correspondence between elevated flortaucipir PET signal and elevated signal on amyloid PET.
“These results are consistent with previously observed correspondence between elevated flortaucipir PET signal and elevated signal on amyloid PET.23,45”
From Positron Emission Tomography Imaging With [ <sup>18</sup> F]flortaucipir and Postmortem Assessment of Alzheimer Disease Neuropathologic Changes (2020) · cites this paper as [45]
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References 39 · Cited by 986
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- Authors
- Johnson, K. A., Schultz, A., Betensky, R. A., Becker, J. A., Sepulcre, J., Rentz, D., Mormino, E., Chhatwal, J., Amariglio, R., Papp, K., Marshall, G., Albers, M., Mauro, S., Pepin, L., Alverio, J., Judge, K., Philiossaint, M., Shoup, T., Yokell, D., Dickerson, B., Gomez‐Isla, T., Hyman, B., Vasdev, N., & Sperling, R.
- Affiliations
- Brigham and Women's Hospital (US)
- Harvard University (US)
- Massachusetts General Hospital (US)
- Department of Neurology Boston MA
- Corresponding author
- Johnson, Keith A.
- ORCID
- Venue
- Annals of Neurology
- Publisher
- Wiley
- Published
- 2015-12-15
- Volume
- 79
- Issue
- 1
- Pages
- 110-119
- ISSN
- 0364-5134 (ISSN-L)
- 1531-8249
- PMC
- PMC4738026
- OpenAlex
- W2215958284
- Cited by
- 986
- References
- 39
- Citations by year
- 2026: 51 · 2025: 78 · 2024: 83 · 2023: 78 · 2022: 98 · 2021: 103 · 2020: 109 · 2019: 119 · 2018: 96 · 2017: 98 · 2016: 72 · 2015: 1
- FWCI
- 72.31
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Annals of Neurology (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institutes of Health (5u01ag024904-10)
- National Institute on Aging (U01-AG-024904, K23AG049087, U01AG010483, P50-AG00513421, R01AG046396, R01AG027435, R01AG037497, P50AG005134, U19AG010483, P01AG036694)
- National Center for Research Resources (M01RR002635)
- Topics
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Health Sciences › Medicine › Radiology, Nuclear Medicine and Imaging › Medical Imaging Techniques and Applications
- Keywords
- tau PET, amyloid PET, Pittsburgh compound B, Alzheimer's disease, mild cognitive impairment, early Alzheimer's disease, inferior temporal gyrus, tau deposition, aging, biomarkers, disease progression
- MeSH terms
- Aged, Aged, 80 and over, Aging, Alzheimer Disease, Aniline Compounds, Carbolines, Cerebral Cortex, Female, Humans, Male, Middle Aged, Temporal Lobe, Thiazoles, Biomarkers, Amyloid beta-Peptides, tau Proteins, Positron-Emission Tomography, Cognitive Dysfunction
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