Progressive Tau Accumulation in Alzheimer Disease: 2-Year Follow-up Study
Open accessAbstract
Tau PET enables in vivo visualization and quantitation of tau accumulation in Alzheimer disease (AD). In cross-sectional tau PET studies, tau burden reflects disease severity and phenotypic variation. We investigated longitudinal changes in cortical tau accumulation and their association with cognitive decline in patients with AD. Methods: We enrolled 107 participants (45 amyloid-β–negative cognitively unimpaired [CU−], 7 amyloid-β–positive cognitively unimpaired [CU+], 31 with prodromal AD [mild cognitive impairment; MCI+], and 24 with AD dementia [DEM+]) who completed 2 baseline PET scans (18F-flortaucipir and 18F-florbetaben), MRI, and neuropsychologic tests. All participants underwent the same assessments after 2 y. After correcting for partial-volume effect, we created SUV ratio (SUVR) images. By using a linear mixed-effect model, we investigated the changes in SUVR across time within each group. We also investigated a correlation between the progression of tau accumulation and cognitive decline. Results: In contrast to no change in global cortical SUVR in the CU− and CU+ groups during the 2-y period, global cortical SUVR increased by 0.06 (2.9%) in the MCI+ group and 0.19 (8.0%) in the DEM+ group at follow-up. The MCI+ group was associated with additional tau accumulation predominantly in the medial and inferior temporal cortices, whereas the DEM+ group showed increases in the lateral temporal cortex. Progressive tau accumulation occurred in the diffuse cortical areas in the MCI+ patients who developed dementia and the DEM+ patients who showed deterioration of global cognition, whereas there was only a small increase of additional tau accumulation in the lateral temporal cortex in those who did not show worsening of cognition. Deterioration of global cognition and language functions was associated with progression of diffuse tau accumulation in the association neocortex. Conclusion: Progressive tau accumulation occurs in prodromal AD and DEM patients in the cortical areas at different levels of tau accumulation. Progression of cognitive dysfunction may be related to the additional tau accumulation in regions of higher Braak stage. 18F-flortaucipir PET is an imaging biomarker for monitoring the progression of AD.
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Cross-sectional and longitudinal human cohort biomarker studies support a scenario in which amyloid pathology precedes tau pathology and then neurodegeneration.
“In contrast, cross-sectional and longitudinal human cohort studies of biomarkers support a scenario in which amyloid pathology (Aβ42 lowering in CSF, positive amyloid PET imaging) precedes tau pathology (tau-PET and phospho-Tau elevation in CSF) and then neurodegeneration 126-128 .”
From The amyloid hypothesis in Alzheimer disease: new insights from new therapeutics (2022) · cites this paper as [126]
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- Authors
- Cho, H., Choi, J. Y., Lee, H. S., Lee, J. H., Ryu, Y. H., Lee, M. S., Jack, C. R., & Lyoo, C. H.
- Affiliations
- Yonsei University (KR)
- Mayo Clinic (US)
- ORCID
- Venue
- Journal of Nuclear Medicine
- Publisher
- Society of Nuclear Medicine
- Published
- 2019-03-29
- Volume
- 60
- Issue
- 11
- Pages
- 1611-1621
- ISSN
- 0161-5505 (ISSN-L)
- 2159-662X
- PMC
- PMC6836867
- OpenAlex
- W2925737272
- Cited by
- 94
- References
- 35
- Citations by year
- 2026: 4 · 2025: 8 · 2024: 8 · 2023: 15 · 2022: 14 · 2021: 28 · 2020: 13 · 2019: 4
- FWCI
- 11.75
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Journal of Nuclear Medicine (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- YUHSpace (Yonsei University Medical Library) (submittedVersion, cc-by-nc-nd)
- 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
- Alzheimer's disease, tau accumulation, 18F-flortaucipir, 18F-florbetaben, cognitive decline, mild cognitive impairment, prodromal Alzheimer's disease, Braak stages, imaging biomarkers, temporal lobe, language loss
- MeSH terms
- Aged, Alzheimer Disease, Atrophy, Biological Transport, Carbolines, Cognition, Female, Follow-Up Studies, Humans, Image Processing, Computer-Assisted, Male, Neuropsychological Tests, tau Proteins, Disease Progression, Positron-Emission Tomography
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