Regional profiles of the candidate tau PET ligand 18 F-AV-1451 recapitulate key features of Braak histopathological stages
Abstract
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…
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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 [134]
The middle temporal gyrus is a transition zone between aging-related or preclinical AD-related medial temporal lobe pTau and more advanced stages of AD, where neocortical pTau extends across the brain and is strongly correlated with dementia.
“Many studies, from the histopathology of Braak and Braak4 to longitudinal studies of Tau positron emission tomography imaging27,28, demonstrate that MTG is a transition zone between aging-related or preclinical AD-related medial temporal lobe pTau and more advanced stages of AD, where neocortical pTau extends across the brain and is strongly correlated with dementia4,29–31.”
From Integrated multimodal cell atlas of Alzheimer’s disease (2024) · cites this paper as [27]
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- Authors
- Schwarz, A. J., Yu, P., Miller, B. B., Shcherbinin, S., Dickson, J., Navitsky, M., Joshi, A. D., Devous, M. D., & Mintun, M. S.
- Affiliations
- Eli Lilly (United States) (US)
- Avid Radiopharmaceuticals (United States) (US)
- Venue
- Brain
- Publisher
- Oxford University Press (OUP)
- Published
- 2016-03-02
- Volume
- 139
- Issue
- 5
- Pages
- 1539-1550
- ISSN
- 0006-8950 (ISSN-L)
- 1460-2156
- OpenAlex
- W2288973352
- Cited by
- 425
- References
- 10
- Citations by year
- 2026: 13 · 2025: 21 · 2024: 27 · 2023: 32 · 2022: 42 · 2021: 52 · 2020: 36 · 2019: 56 · 2018: 61 · 2017: 62 · 2016: 21 · 2015: 1
- FWCI
- 59.24
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Brain (publishedVersion)
- PubMed (publishedVersion)
- HighWire Press Open Archive (submittedVersion)
- 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
- 18F-AV-1451, tau PET, Braak staging, neurofibrillary tangles, Alzheimer's disease, mild cognitive impairment, amyloid status, hippocampal sparing, tau PET tracers
- MeSH terms
- Adult, Aged, Aged, 80 and over, Algorithms, Alzheimer Disease, Carbolines, Female, Humans, Male, Middle Aged, Occipital Lobe, Severity of Illness Index, Temporal Lobe, Neurofibrillary Tangles, tau Proteins, Positron-Emission Tomography, Young Adult, Neuroimaging, Cognitive Dysfunction
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