ArticleEuropean journal of nuclear medicine and molecular imaging2021
Indication of retrograde tau spreading along Braak stages and functional connectivity pathways.
Article in European journal of nuclear medicine and molecular imaging, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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15 citing papers in PubMed, 18 citations in OpenAlex.
- Cyclic 2.5D Perceptual Loss for Cross-Modal 3D Medical Image Synthesis: T1w MRI to Tau PET.Human brain mapping · 2026Article
- Adaptive Integration of Incomplete Multimodal 3D Neuroimaging for Alzheimer's Prediction and Biomarker Discovery.AMIA Joint Summits on Translational Science proceedings. AMIA Joint Summits on Translational Science · 2026Article
- Hyperactive neuronal networks enhance tau spread in an Alzheimer's disease mouse model.bioRxiv : the preprint server for biology · 2025Article
- Tau profiling across Alzheimer's disease staging reveals vulnerability to disease pathophysiology.European journal of nuclear medicine and molecular imaging · 2025Article
- Exploring the origins of frequent tau-PET signal in vermal and adjacent regions.European journal of nuclear medicine and molecular imaging · 2025Article
- The Bidirectional Relationship Between Epilepsy and Alzheimer's Disease.Current neurology and neuroscience reports · 2025Review
- Neuronal activity induces symmetry breaking in neurodegenerative disease spreading.Journal of mathematical biology · 2024Article
- The Alzheimer's Disease Neuroimaging Initiative in the era of Alzheimer's disease treatment: A review of ADNI studies from 2021 to 2022.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2024Review
- Biostatistical Estimation of Tau Threshold Hallmarks (BETTH) Algorithm for Human Tau PET Imaging Studies.Journal of nuclear medicine : official publication, Society of Nuclear Medicine · 2023Article
- The Use of Tau PET to Stage Alzheimer Disease According to the Braak Staging Framework.Journal of nuclear medicine : official publication, Society of Nuclear Medicine · 2023Review
- Molecular pathology and synaptic loss in primary tauopathies: an 18F-AV-1451 and 11C-UCB-J PET study.Brain : a journal of neurology · 2022Observational
- Imaging Clinical Subtypes and Associated Brain Networks in Alzheimer's Disease.Brain sciences · 2022Review
- Review
- Alzheimer's disease is an inherent, natural part of human brain aging: an integrated perspective.Free neuropathology · 2022Article
- Article
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Authors and funding
7 authors at 3 institutions in 3 countries.
Funding
Abstract
purposeTau pathology progression in Alzheimer's disease (AD) is explained through the network degeneration hypothesis and the neuropathological Braak stages; however, the compatibility of these models remains unclear.
methodsWe utilized [18F]AV-1451 tau-PET scans of 39 subjects with AD and 39 sex-matched amyloid-negative healthy controls (HC) in the ADNI (Alzheimer's Disease Neuroimaging Initiative) dataset. The peak cluster of tau-tracer uptake was identified in each Braak stage of neuropathological tau deposition and used to create a seed-based functional connectivity network (FCN) using 198 HC subjects, to identify healthy networks unaffected by neurodegeneration.
resultsVoxel-wise tau deposition was both significantly higher inside relative to outside FCNs and correlated significantly and positively with levels of healthy functional connectivity. Within many isolated Braak stages and regions, the correlation between tau and intrinsic functional connectivity was significantly stronger than it was across the whole brain. In this way, each peak cluster of tau was related to multiple Braak stages traditionally associated with both earlier and later stages of disease.
conclusionWe show specificity of healthy FCN topography for AD-pathological tau as well as positive voxel-by-voxel correlations between pathological tau and healthy functional connectivity. We propose a model of "up- and downstream" functional tau progression, suggesting that tau pathology evolves along functional connectivity networks not only "downstream" (i.e., along the expected sequence of the established Braak stages) but also in part "upstream" or "retrograde" (i.e., against the expected sequence of the established Braak stages), with pathology in earlier Braak stages intensified by its functional relationship to later disease stages.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.