Staging Alzheimer's disease through amyloid and tau PET.
Overview
- Department of Radiology, Mayo Clinic, Rochester, MN 55905, USA
- Department of Quantitative Health Sciences, Mayo Clinic, Rochester, MN 55905, USA
- Department of Neurology, Mayo Clinic, Rochester, MN 55905, USA
- Department of Information Technology, Mayo Clinic, Rochester, MN 55905, USA
- Department of Data Science, University of Mississippi Medical Center, Jackson, MS 39216, USA
Abstract
A workgroup assembled by the Alzheimer’s Association recently described a conceptual framework for Alzheimer’s disease biological staging based on amyloid and tau PET imaging. However, specific tau PET cut points were left to be determined, a step necessary prior to clinical application. We sought to operationalize and evaluate Alzheimer’s disease biological staging by identifying meaningful tau PET cut points to define the four biological stages in a well-characterized participant cohort and describe the features of individuals placed into the different biological stages.
The primary analysis included 896 participants in the Mayo Clinic Study of Aging or the Mayo Clinic Alzheimer’s Disease Research Center longitudinal cohorts. A validation cohort consisted of 328 participants in the Alzheimer’s Disease Neuroimaging Initiative. Both cognitively normal and impaired individuals with positive amyloid PET and evaluable tau PET imaging were included. Tau PET cut points were identified with Gaussian mixture models to characterize Alzheimer’s disease biological stage in study participants with different clinical diagnoses and objective degrees of cognitive impairment as measured by Mini-Mental State Examination.
A tau PET cut point in the medial temporal region and two cut points in the temporoparietal region were identified to produce, collectively, the four Alzheimer’s disease biological stages described in the revised criteria. Increasing stage was associated with greater likelihood of mild cognitive impairment and dementia diagnosis and worsening cognitive performance on Mini-Mental State Examination and Clinical Dementia Rating Sum of Boxes, a result that was reproduced in the independent Alzheimer’s Disease Neuroimaging Initiative cohort.
This study provided empirical validation for the concept of using amyloid PET and tau PET to separate subjects with biomarker-proven Alzheimer’s disease into four biological stages with distinct characteristics.
Reproduced under the paper's license (CC BY-NC), from the paper cited above.
Code
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Data
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Data availability
Data from the Mayo cohort are available to qualified academic and industry researchers by request to the MCSA and ADRC Executive Committee (https://
Reproduced under the paper's license (CC BY-NC), from the paper cited above.
Versions
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Version 1, 30 September 2026: the first record
Recorded: type, language, journal, volume, issue, pages, dates, 16 authors, 3 keywords, 14 MeSH terms, 11 funders, 35 references.
Cite
This paper
Johnson, D. R., Wiste, H. J., Lowe, V., Schwarz, C. G., Knopman, D. S., Vemuri, P., Kantarci, K., Boeve, B. F., Graff-Radford, J., Cogswell, P. M., Senjem, M. C., Therneau, T. M., Griswold, M. E., Hu, M., Petersen, R. C., & Jack, C. R. (2026). Staging Alzheimer's disease through amyloid and tau PET. Brain : a journal of neurology, 149(3), 1023-1034. https://
BibTeX
@article{johnson2026stag
author = {Johnson, Derek R and Wiste, Heather J and Lowe, Val and Schwarz, Christopher G and Knopman, David S and Vemuri, Prashanthi and Kantarci, Kejal and Boeve, Bradley F and Graff-Radford, Jonathan and Cogswell, Petrice M and Senjem, Matthew C and Therneau, Terry M and Griswold, Michael E and Hu, Mingzhao and Petersen, Ronald C and Jack, Clifford R},
title = {{Staging Alzheimer's disease through amyloid and tau PET}},
journal = {Brain : a journal of neurology},
year = {2026},
month = mar,
volume = {149},
number = {3},
pages = {1023--1034},
publisher = {Oxford University Press},
issn = {0006-8950},
doi = {10.1093/
url = {https://
pmid = {40974012},
pmcid = {PMC13016809}
}
RIS
TY - JOUR
AU - Johnson, Derek R
AU - Wiste, Heather J
AU - Lowe, Val
AU - Schwarz, Christopher G
AU - Knopman, David S
AU - Vemuri, Prashanthi
AU - Kantarci, Kejal
AU - Boeve, Bradley F
AU - Graff-Radford, Jonathan
AU - Cogswell, Petrice M
AU - Senjem, Matthew C
AU - Therneau, Terry M
AU - Griswold, Michael E
AU - Hu, Mingzhao
AU - Petersen, Ronald C
AU - Jack, Clifford R
TI - Staging Alzheimer's disease through amyloid and tau PET
T2 - Brain : a journal of neurology
J2 - Brain
PY - 2026
DA - 2026/
VL - 149
IS - 3
SP - 1023
EP - 1034
SN - 0006-8950
PB - Oxford University Press
DO - 10.1093/
UR - https://
LA - en
ER -
CSL-JSON
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