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Regional profiles of the candidate tau PET ligand 18F-AV-1451 recapitulate key features of Braak histopathological stages
Schwarz AJ, Yu P, Miller BB, Shcherbinin S, Dickson J, Navitsky M, Joshi AD, Devous MD et al.. Brain : a journal of neurology, 2016-03-02
Topic: Brain proteins, microglia and lab models
SEE THAL AND VANDENBERGHE DOI101093/BRAIN/AWW057 FOR A SCIENTIFIC COMMENTARY ON THIS ARTICLE: Post-mortem Braak staging of neurofibrillary tau tangle topographical distribution is one of the core neuropathological criteria for the diagnosis of Alzheimer's disease. The recent development of positron emission tomography tracers targeting neurofibrillary tangles has enabled the distribution of tau pathology to be imaged in living subjects. Methods for extraction of classic Braak staging from in vivo imaging of neurofibrillary tau tangles have not yet been explored. Standardized uptake value ratio images were calculated from 80-100 minute (18)F-AV-1451 (also known as T807) positron emission tomography scans obtained from n = 14 young reference subjects (age 21-39 years, Mini-Mental State Examination 29-30) and n = 173 older test subjects (age 50-95 years) comprising amyloid negative cognitively normal (n = 42), clinically-diagnosed mild cognitive impairment (amyloid positive, n = 47, and amyloid negative, n = 40) and Alzheimer's disease (amyloid positive, n = 28, and amyloid negative, n = 16). We defined seven regions of interest in anterior temporal lobe and occipital lobe sections corresponding closely to those used as decision points in Braak staging. An algorithm based on the Braak histological staging procedure was applied to estimate Braak stages directly from the region of interest profiles in each subject. Quantitative region-based analysis of (18)F-AV-1451 images yielded region of interest and voxel level profiles that mirrored key features of neuropathological tau progression including profiles consistent with Braak stages 0 through VI. A simple set of decision rules enabled plausible Braak stages corresponding to stereotypical progression patterns to be objectively estimated in 149 (86%) of test subjects. An additional 12 (7%) subjects presented with predefined variant profiles (relative sparing of the hippocampus and/or occipital lobe). The estimated Braak stage was significantly associated with amyloid status, diagnostic category and measures of global cognition. In vivo (18)F-AV-1451 positron emission tomography images across the Alzheimer's disease spectrum could be classified into patterns similar to those prescribed by Braak neuropathological staging of tau pathology.
Key findings
- The estimated Braak stage was significantly associated with amyloid status, diagnostic category and measures of global cognition.
Why it matters
In 173 older adults ranging from cognitively normal to Alzheimer's disease, scans with the tau PET tracer 18F-AV-1451 could be sorted into patterns resembling the Braak stages that pathologists use after death: a simple set of rules gave a "plausible" stage for 149 people (86%), and 12 more (7%) showed predefined variant patterns. The estimated stage was significantly associated with amyloid status, diagnosis and global cognition. The study reports no comparison with autopsy and no follow-up scans, so it shows that tau PET can look like Braak staging, not that it measures a person's stage. It is an imaging method, not a treatment.
Study details
- Participants14
- Evidence strengthLow
How this study scored 58/100
Published in a leading specialty journal. Scored zero for study design, effect reported and randomised / blinded because the record does not state it. We have no data on senior author's track record, so that was left out: it earned 56 of the 96 points we could judge it on, which is 58 out of 100.
| Component | Points | Why |
|---|---|---|
| Journal tier | 9 / 10 | Tier 2 — leading specialty journal (Brain : a journal of neurology) |
| Journal's citation record | 4 / 4 | Brain: journal h-index 503 (OpenAlex, 2026-10-29) |
| Study design | 0 / 12 | No study design recorded — scores zero, not guessed (not stated in the record — scored 0) |
| Strength of evidence | 1 / 5 | Rated “low” in our summary |
| Peer-review validation | 10 / 10 | Peer-reviewed. Published as an article in a named peer-reviewed journal. |
| How recent | 1 / 5 | 2016 — within 20 year(s) of the newest study here |
| Sample size | 1 / 4 | 14 participants |
| Effect reported | 0 / 3 | No effect size reported — scores zero (not stated in the record — scored 0) |
| Studied in people | 3 / 3 | Studied in people (participant count stated) |
| Randomised / blinded | 0 / 2 | No randomisation or blinding stated — scores zero (not stated in the record — scored 0) |
| Times cited | 6 / 7 | Cited 426 times (OpenAlex, 2026-10-10) |
| Citations per year | 4 / 5 | 35.5 citations a year over 12 year(s) since 2016 |
| Impact for its field and year | 6 / 6 | Cited 52.1× the average for papers of its field and year (OpenAlex FWCI) |
| Cited by studies here | 4 / 6 | Cited by 44 other studies in this library |
| Still being cited | 3 / 4 | Cited 58 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | — / 4 | OpenAlex's profile for last-listed author Mark S. Mintun holds only 1 work(s), too few to judge a track record — left out of this score |
| Institution's track record | 1 / 3 | Eli Lilly (United States): institution h-index 744 (OpenAlex) |
| Multi-centre collaboration | 1 / 3 | OpenAlex lists 2 institution(s) in 1 country |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 26936940) |
| Free to read | 0 / 2 | Behind a paywall — scores zero |
| Points | 56 / 96 | Scored on 19 of 20 parts. We have no data for the rest, so they are left out: 56 of the 96 points we could judge it on is 58 out of 100. |
| Total | 58 / 100 | — |
What each of these 20 components measures, and what this score is not →
Read the original
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Cite this study APA, Vancouver, BibTeX · download .bib or .ris
Built from the record alzhub holds for this paper, not looked up. Volume, issue and page numbers are not held in the record. The record's author list ends in “et al.”, so not every author is named. Check the citation against the original before you use it.
APA 7th
Schwarz, A. J., Yu, P., Miller, B. B., Shcherbinin, S., Dickson, J., Navitsky, M., et al. (2016). Regional profiles of the candidate tau PET ligand 18F-AV-1451 recapitulate key features of Braak histopathological stages. Brain : a journal of neurology. https://doi.org/10.1093/brain/aww023
Vancouver
Schwarz AJ, Yu P, Miller BB, Shcherbinin S, Dickson J, Navitsky M, et al. Regional profiles of the candidate tau PET ligand 18F-AV-1451 recapitulate key features of Braak histopathological stages. Brain : a journal of neurology. 2016. doi:10.1093/brain/aww023. PMID: 26936940.
BibTeX
@article{schwarz2016-26936940,
author = {Schwarz, A. J. and Yu, P. and Miller, B. B. and Shcherbinin, S. and Dickson, J. and Navitsky, M. and Joshi, A. D. and Devous, M. D. and others},
title = {{Regional profiles of the candidate tau PET ligand 18F-AV-1451 recapitulate key features of Braak histopathological stages}},
journal = {Brain : a journal of neurology},
year = {2016},
doi = {10.1093/brain/aww023},
pmid = {26936940},
url = {https://doi.org/10.1093/brain/aww023}
}
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