Comparison of multiple tau-PET measures as biomarkers in aging and Alzheimer's disease
Open accessAbstract
The recent development of tau-specific positron emission tomography (PET) tracers enables in vivo quantification of regional tau pathology, one of the key lesions in Alzheimer's disease (AD). Tau PET imaging may become a useful biomarker for clinical diagnosis and tracking of disease progression but there is no consensus yet on how tau PET signal is best quantified. The goal of the current study was to evaluate multiple whole-brain and region-specific approaches to detect clinically relevant tau PET signal. Two independent cohorts of cognitively normal adults and amyloid-positive (Aβ+) patients with mild cognitive impairment (MCI) or AD-dementia underwent [18 F]AV-1451 PET. Methods for tau tracer quantification included: (i) in vivo Braak staging, (ii) regional uptake in Braak composite regions, (iii) several whole-brain measures of tracer uptake, (iv) regional uptake in AD-vulnerable voxels, and (v) uptake in a priori defined regions. Receiver operating curves characterized accuracy in distinguishing Aβ- controls from AD/MCI patients and yielded tau positivity cutoffs. Clinical relevance of tau PET measures was assessed by regressions against cognition and MR imaging measures. Key tracer uptake patterns were identified by a factor analysis and voxel-wise contrasts. Braak staging, global and region-specific tau measures yielded similar diagnostic accuracies, which differed between cohorts. While all tau measures were related to amyloid and global cognition, memory and hippocampal/entorhinal volume/thickness were associated with regional tracer retention in the medial temporal lobe. Key regions of tau accumulation included medial temporal and inferior/middle temporal regions, retrosplenial cortex, and banks of the superior temporal sulcus. Our data indicate that whole-brain tau PET measures might be adequate biomarkers to detect AD-related tau pathology. However, regional measures covering AD-vulnerable regions may increase sensitivity to early tau PET signal, atrophy and memory decline.
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The 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 [16]
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Cites
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- Authors
- Maass, A., Landau, S., Baker, S. L., Horng, A., Lockhart, S. N., La Joie, R., Rabinovici, G. D., & Jagust, W. J.
- Affiliations
- German Center for Neurodegenerative Diseases (DE)
- University of California, Berkeley (US)
- Lawrence Berkeley National Laboratory (US)
- Corresponding author
- Maass, Anne
- ORCID
- Venue
- NeuroImage
- Publisher
- Elsevier BV
- Published
- 2017-08
- Volume
- 157
- Pages
- 448-463
- ISSN
- 1053-8119 (ISSN-L)
- PMC
- PMC5814575
- OpenAlex
- W2621105275
- Cited by
- 462
- References
- 12
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- FWCI
- 34.16
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- NeuroImage (acceptedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- eScholarship (California Digital Library) (submittedVersion)
- OSTI OAI (U.S. Department of Energy Office of Scientific and Technical Information) (submittedVersion)
- DZNE Pub (submittedVersion)
- Funders
- University of California, San Diego
- Eli Lilly and Company
- Biogen
- National Institute of Biomedical Imaging and Bioengineering
- Alzheimer's Disease Neuroimaging Initiative
- Northern California Institute for Research and Education
- University of Southern California
- U.S. Department of Defense (W81XWH-12-2-0012)
- Alzheimer's Association
- Roche
- National Institute on Aging
- AbbVie
- Alzheimer's Drug Discovery Foundation
- National Institutes of Health (U01 AG024904)
- Bristol-Myers Squibb
- Eisai
- BioClinica
- 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, Alzheimer's disease, mild cognitive impairment, 18F-AV-1451, Braak staging, tau biomarkers, amyloid, medial temporal lobe, entorhinal cortex, hippocampal atrophy, memory decline, diagnostic accuracy, aging
- MeSH terms
- Adult, Aged, Aged, 80 and over, Aging, Alzheimer Disease, Carbolines, Female, Humans, Male, Middle Aged, Severity of Illness Index, Cohort Studies, Amyloid beta-Peptides, tau Proteins, Age of Onset, Neocortex, Positron-Emission Tomography, Young Adult, Cognitive Dysfunction
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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