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Tau seeding activity begins in the transentorhinal/entorhinal regions and anticipates phospho-tau pathology in Alzheimer’s disease and PART
Open accessPublished version of a preprint
Abstract
Alzheimer's disease (AD) is characterized by accumulation of tau neurofibrillary tangles (NFTs) and, according to the prion model, transcellular propagation of pathological "seeds" may underlie its progression. Staging of NFT pathology with phospho-tau antibody is useful to classify AD and primary age-related tauopathy (PART) cases. The locus coeruleus (LC) shows the earliest phospho-tau signal, whereas other studies suggest that pathology begins in the transentorhinal/entorhinal cortices (TRE/EC). The relationship of tau seeding activity, phospho-tau pathology, and progression of neurodegeneration remains obscure. Consequently, we employed an established cellular biosensor assay to quantify tau seeding activity in fixed human tissue, in parallel with AT8 phospho-tau staining of immediately adjacent sections. We studied four brain regions from each of n = 247 individuals across a range of disease stages. We detected the earliest and most robust seeding activity in the TRE/EC. The LC did not uniformly exhibit seeding activity until later NFT stages. We also detected seeding activity in the superior temporal gyrus (STG) and primary visual cortex (VC) at stages before NFTs and/or AT8-immunopositivity were detectable. AD and putative PART cases exhibited similar patterns of seeding activity that anticipated histopathology across all NFT stages. Our findings are consistent with the prion model and suggest that pathological seeding activity begins in the TRE/EC rather than in the LC. In the analysis of tauopathy, quantification of seeding activity may offer an important addition to classical histopathology.
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“Several studies have shown that seeding precedes tau pathogenesis and can even occur in brain regions where tau pathology does not usually present (DeVos et al., 2018; Kaufman et al., 2018; Stopschinski et al., 2021).”
From Network analysis identifies strain-dependent response to tau and tau seeding-associated genes (2023) · cites this paper as Kaufman et al., 2018
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Citations
Cites
Neuropathological stageing of Alzheimer-related changes.
Braak, H., & Braak, E. (1991) · Acta Neuropathologica · doi:10.1007/bf00308809 · Cited by 16,123 · cited 2×
“This tau pathology has a characteristic regional pattern of progression, thereby permitting the distinction of different stages in asymptomatic and symptomatic individuals [4, 8].”
BackgroundSelf-citationStaging of brain pathology related to sporadic Parkinson’s disease
Braak, H., Tredici, K. D., Rüb, U., de Vos, R. A. I., Jansen Steur, E. N. H., & Braak, E. (2003) · Neurobiology of Aging · doi:10.1016/s0197-4580(02)00065-9 · Cited by 10,777
Self-citationAmyloid oligomers exacerbate tau pathology in a mouse model of tauopathy
Selenica, M.-L. B., Brownlow, M., Jimenez, J. P., Lee, D. C., Pena, G., Dickey, C. A., Gordon, M. N., & Morgan, D. (2013) · Neurodegenerative Diseases · doi:10.1159/000337230 · Cited by 10,359
Phases of Aβ-deposition in the human brain and its relevance for the development of AD
Thal, D. R., Rüb, U., Orantes, M., & Braak, H. (2002) · Neurology · doi:10.1212/wnl.58.12.1791 · Cited by 3,490
Self-citationBraak, H., Alafuzoff, I., Arzberger, T., Kretzschmar, H., & Del Tredici, K. (2006) · Acta Neuropathologica · doi:10.1007/s00401-006-0127-z · Cited by 3,172
Self-citationHyman, B. T., Phelps, C. H., Beach, T. G., Bigio, E. H., Cairns, N. J., Carrillo, M. C., Dickson, D. W., Duyckaerts, C., Frosch, M. P., Masliah, E., et al. (2012) · Alzheimer's & Dementia · doi:10.1016/j.jalz.2011.10.007 · Cited by 3,092
Lee, V. M.-Y., Goedert, M., & Trojanowski, J. Q. (2001) · Annual Review of Neuroscience · doi:10.1146/annurev.neuro.24.1.1121 · Cited by 2,480
Staging of alzheimer's disease-related neurofibrillary changes
Braak, H., & Braak, E. (1995) · Neurobiology of Aging · doi:10.1016/0197-4580(95)00021-6 · Cited by 2,357
Self-citationPan, K. M., Baldwin, M. A., Nguyen, J. T., Gasset, M., Serban, A. V., Groth, D., Mehlhorn, I., Huang, Z., Fletterick, R. J., & Cohen, F. E. (1993) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.90.23.10962 · Cited by 2,281
Stages of the Pathologic Process in Alzheimer Disease: Age Categories From 1 to 100 Years
Braak, H., Thal, D. R., Ghebremedhin, E., & Del Tredici, K. (2011) · Journal of Neuropathology & Experimental Neurology · doi:10.1097/nen.0b013e318232a379 · Cited by 2,194
Self-citation
Flagged first, then by citations
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Items 201–259 of 259
Parfyonov, D., Wang, X., Barker, S., Corey, D. A., Vázquez‐Rosa, E., Abeyesundere, N., Ward, W. M., Darrah, R. J., Woo, J. A., Kang, D. E., et al. (2025) · Journal of Cystic Fibrosis · doi:10.1016/j.jcf.2025.04.003 · Cited by 3
Luan, Y., Zheng, L., Denecke, J., Dehsarvi, A., Roemer, S. N., Dewenter, A., Steward, A., Shcherbinin, S., Svaldi, D. O., Kotari, V., et al. (2025) · Alzheimer s & Dementia · doi:10.1002/alz.70170 · Cited by 3
Fyn-dependent Tau microcluster formation seeds and boosts extensive Tau pathology
Li, Y., Qi, W., Chen, L., Chu, F., Jiang, W., Xu, Z., Luo, Y., Hu, X., Götz, J., & Li, C. (2025) · Acta Neuropathologica · doi:10.1007/s00401-025-02887-2 · Cited by 3
Datta, D. (2023) · The Journals of Gerontology Series A · doi:10.1093/gerona/glad134 · Cited by 3
Teng, J., McKenna, M. R., Gbadeyan, O., Prakash, R. S., & Initiative, A. D. N. (2024) · Network Neuroscience · doi:10.1162/netn_a_00373 · Cited by 6
Tau Pathology in Neurodegenerative Diseases
Vogels, T., & Hromádka, T. (2021) · Neuromethods · doi:10.1007/978-1-0716-1712-0_4 · Cited by 2
How Many Alzheimer–Perusini’s Atypical Forms Do We Still Have to Discover?
Donato, L., Mordà, D., Scimone, C., Alibrandi, S., D’Angelo, R., & Sidoti, A. (2023) · Biomedicines · doi:10.3390/biomedicines11072035 · Cited by 3
Memory, Sleep, and Tau Function
Ávila, J., & Perry, G. L. (2023) · Journal of Alzheimer s Disease · doi:10.3233/jad-230230 · Cited by 3
Alzheimer mimicry: LATE and PART
Bogdanović, N., Smailović, U., & Jelić, V. (2025) · Journal of Neural Transmission · doi:10.1007/s00702-025-02916-0 · Cited by 3
Ramani, B., Ehsani, K., & Kampmann, M. (2026) · Journal of Biological Chemistry · doi:10.1016/j.jbc.2026.111292 · Cited by 2
The nucleus locus coeruleus modulatory effect on memory formation: A literature review
Khakpour-Taleghani, B., Akhoondian, M. J., & Jafari, A. (2021) · Journal of Current Biomedical Reports · doi:10.52547/jcbior.2.4.142 · Cited by 2
In situ seeding assay: A novel technique for direct tissue localization of bioactive tau
Perbet, R., de Gérando, A. M., Glynn, C. A., Donahue, C., Gaona, A., Taddei, R. N., Gómez‐Isla, T., Lathuilière, A., & Hyman, B. T. (2024) · Journal of Neuropathology & Experimental Neurology · doi:10.1093/jnen/nlae059 · Cited by 2
A lipid-raft theory of Alzheimer's disease
Rappoport, A. (2025) · Elsevier eBooks · doi:10.1016/b978-0-44-345008-2.00017-5 · Cited by 2
Tau seeding starts early in the entorhinal cortex
Ridler, C. E. (2018) · Nature Reviews Neurology · doi:10.1038/s41582-018-0016-9 · Cited by 2
Ramsden, C. E., Zamora, D., Horowitz, M. S., Jahanipour, J., Keyes, G. S., Li, X., Murray, H. C., Curtis, M. A., Faull, R. L. M., Sedlock, A. B., et al. (2023) · medRxiv · doi:10.21203/rs.3.rs-2968020/v1 · Cited by 2
Rodriguez‐Rodriguez, P., Wang, W., Tsagkogianni, C., Feng, I., Morello-Megias, A., Jain, K., Alanko, V., Kahvecioglu, H. A., Mohammadi, E., Li, X., et al. (2025) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2024.12.31.630881 · Cited by 2
Sivanesan, S., Howell, M. D., Kaushik, V., Rajadas, J., Pari, S. S., & Goyal, P. (2024) · Current Alzheimer Research · doi:10.2174/0115672050324909240823104209 · Cited by 1
Liu, H., Liu, X., Tian, F., Chen, Y., Li, J., Wang, X., Qiu, W., Wang, X., Ma, C., & Ge, W. (2025) · Advanced Science · doi:10.1002/advs.202506044 · Cited by 1
Burst firing in Alzheimer’s disease: A shift beyond amyloid?
Lopes, L. V., & Pousinha, P. A. (2025) · Cell · doi:10.1016/j.cell.2025.06.016 · Cited by 1
Malarte, M., Chiotis, K., Ioannou, K., & Rodriguez‐Vieitez, E. (2025) · Journal of Neurochemistry · doi:10.1111/jnc.70222 · Cited by 2
Fully individualized models for cross-sectional and longitudinal network-based tau spread
Brown, C., Das, S. R., Detre, J. A., Nasrallah, I. M., Yushkevich, P. A., McMillan, C. T., & Wolk, D. A. (2025) · Imaging Neuroscience · doi:10.1162/imag.a.1053 · Cited by 1
Rani, N., Moghekar, A., Callow, D. D., Alm, K. H., Pettigrew, C. A., Soldan, A., Miller, M. H., Wang, J., Lodge, M. A., Albert, M., et al. (2026) · Neurology · doi:10.1212/wnl.0000000000214620 · Cited by 1
Datta, D., Wang, M., & Arnsten, A. F. T. (2026) · Frontiers in Cellular Neuroscience · doi:10.3389/fncel.2026.1750092 · Cited by 1
Zamani, J., Vahid, A., Wilson, E. N., Hosseini, S. M. H., & Initiative, T. F. L. D. N. (2026) · Alzheimer s & Dementia · doi:10.1002/alz.71265 · Cited by 1
Tau burden across Braak stages is associated with regionally specific amyloid accumulation
Rani, N., Alm, K. H., Callow, D. D., Zhu, Y., Pettigrew, C. A., Soldan, A., Lodge, M. A., Miller, M., Albert, M., & Bakker, A. (2026) · Brain Communications · doi:10.1093/braincomms/fcag184 · Cited by 1
Molecular Mechanisms Encoding Strains of Prions and Prion-Like Misfolded Proteins
Hromádková, L., Siddiqi, M. K., Liu, H., & Safar, J. (2023) · Springer eBooks · doi:10.1007/978-3-031-20565-1_7 · Cited by 1
Yoon, S., Kim, H. Y., Park, S., Cha, M., Kim, K., Lee, S., Kim, J., Bhang, S., & Kim, Y. S. (2024) · Angewandte Chemie · doi:10.1002/ange.202411942 · Cited by 1
Apolipoprotein E ε4-Specific Relationship Between Serum Olfactomedin 4 and Alzheimer’s Disease
Wei, C., Zhang, G., Fu, X., Zhao, M. L., Zhai, W., Shen, Y., & Sun, L. (2025) · Molecular Neurobiology · doi:10.1007/s12035-025-04812-w · Cited by 1
Amplification, not spreading limits rate of tau aggregate accumulation in Alzheimer’s diseasePreprint
Meisl, G., Zuo, Y., Allinson, K. S. J., Rittman, T., DeVos, S. L., Sanchez, J. S., Xu, C. K., Duff, K., Johnson, K. A., Rowe, J. B., et al. (2020) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2020.11.16.384727 · Cited by 1
Ziontz, J., Adams, J. N., Harrison, T. M., Baker, S. L., & Jagust, W. J. (2021) · doi:10.21203/rs.3.rs-235539/v1 · Cited by 1
Aberrant medial entorhinal cortex dynamics link tau pathology to spatial memory impairmentPreprint
Malone, T. J., Cekada, K., Tyan, J., Chen, L., Wang, G., & Gu, Y. (2025) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.64898/2025.12.30.696887 · Cited by 1
Catestatin ameliorates tauopathy and amyloidogenesis via adrenergic inhibitionPreprint
Jati, S., Kal, S., Muñoz-Mayorga, D., Tang, K., Sahoo, D., Chen, X., & Mahata, S. K. (2026) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.64898/2026.01.04.697519 · Cited by 1
The Analysis of Exosomal Tau Release and its Regulation
Bradshaw, A. (2018) · UCL Discovery (University College London)
Cappa, S. F. (2020) · Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature · doi:10.3410/f.735988257.793576095
Alzheimer’s disease as a syndrome of overloaded amyloidic synaptic tagging in memory networksPreprint
Murphy, N. (2021) · OSF Preprints (OSF Preprints) · doi:10.31219/osf.io/7gsaz
Rodriguez-Rodriguez, P., Arroyo-García, L., Li, L.-C., Tsagkogianni, C., Wang, W., Salas-Allende, I., Plautz, Z. R., Cedazo-Mínguez, A., Sinha, S. C., Troyanskaya, O., et al. (2022) · bioRxiv · doi:10.1101/2022.05.14.491965
Reyes, I., Faustin, A., Tian, C., & Masurkar, A. V. (2024) · Journal of Neuropsychiatry · doi:10.1176/appi.neuropsych.20230113
Sandberg, A. A., Puttagunta, S., Duval, N., Fleming, H., Koza, L. A., Hieber, K., Holsopple, J., Reyna, M., Paredes, D., & Linseman, D. A. (2025) · Journal of Alzheimer s Disease · doi:10.1177/13872877251338323
Dominguez, P. A., Palpatzis, E., Akinci, M., Canal-García, A., Pereira, J. B., Bejanin, A., & Arenaza‐Urquijo, E. M. (2025) · The Journal of Prevention of Alzheimer s Disease · doi:10.1016/j.tjpad.2025.100294
Prakash, R. S., Phansikar, M., Fisher, M. E., Dove, S., Andridge, R., Scharre, D. W., Wright, K., Head, E., O’Callaghan, C., Meyerson, Q. K., et al. (2025) · doi:10.2196/preprints.86276
Prakash, R. S., Phansikar, M., Fisher, M. E., Dove, S., Andridge, R., Scharre, D. W., Wright, K., Head, E., O’Callaghan, C., Meyerson, Q. K., et al. (2025) · JMIR Research Protocols · doi:10.2196/86276
Benin, B. M., Hillyer, T., Csubak, B. A., Aguirre, N., Crish, S. D., Kang, C., & Shin, W. S. (2025) · Pharmacological Research - Natural Products · doi:10.1016/j.prenap.2025.100449
Bengoa‐Vergniory, N., Velentza‐Almpani, E., Silva, A. M., Scott, C., Vargas‐Caballero, M., Sastre, M., Wade‐Martins, R., & Alegre‐Abarrategui, J. (2021) · Figshare · doi:10.6084/m9.figshare.13663206
Frey, B., Holzinger, D., Taylor, K. C., Ehrnhoefer, D. E., Striebinger, A., Biesinger, S., Gasparini, L., O’Neill, M. J., Wegner, F., Barghorn, S., et al. (2024) · Figshare · doi:10.6084/m9.figshare.26639710
Jin, N., 顾建兰, Wu, R., Chu, D., Tung, Y. C., Węgiel, J., Wisniewski, T., Gong, C.-X., Iqbal, K., & Liu, F. (2022) · Figshare · doi:10.6084/m9.figshare.20968215
Cai, Y., Du, J., Li, A., Zhu, Y., Xu, L., Sun, K., Ma, S., & Guo, T. (2024) · Figshare · doi:10.6084/m9.figshare.26567042
Additional file 1 of Synaptic tau: A pathological or physiological phenomenon?
Robbins, M., Clayton, E. L., & Schierle, G. S. K. (2021) · Figshare · doi:10.6084/m9.figshare.16599510
Stopschinski, B. E., Tredici, K. D., Estill-Terpack, S.-J., Ghebremedhin, E., Yu, F. F., Braak, H., & Diamond, M. I. (2021) · Figshare · doi:10.6084/m9.figshare.16786942
Self-citationVautheny, A. (2019) · theses.fr (ABES) · doi:10.70675/1812d71aze8d9z48d6z87d1z5a23a4e81953
Kozlov, I., Hung, Y.-S., Roy, S., Goud, A. C., Kouřil, R., Wong, Y., & Das, V. (2026) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.64898/2026.04.20.719548
Spatial navigation through evolution: a single-cell atlas of the mammalian entorhinal cortexPreprint
Ralbovszki, D. M., Westfall, J. J., Mori, Y., Tahas, S. A., Bertelsen, M. F., Korshunova, I., Skov, J., Gorodkin, J., Hemberg, M., Seemann, E. S., et al. (2026) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.64898/2026.05.07.723541
Evolution of the Neurometabolic Cascade of Traumatic Brain Injury
Flavin, W. P., Bickart, K. C., Belle, J. E. L., Babikian, T., Harris, M., Kamins, J., Pineda, J. A., Choe, M. C., Giza, C. C., & Prins, M. L. (2026) · Neurologic Clinics · doi:10.1016/j.ncl.2026.05.001
Phillips, W. T., & Schwartz, J. G. (2026) · Frontiers in Neuroscience · doi:10.3389/fnins.2026.1897376
Catestatin peptide ameliorates tauopathy and amyloidogenesis via adrenergic inhibition
Jati, S., Kal, S., Muñoz-Mayorga, D., Tang, K., Sahoo, D., Chen, X., & Mahata, S. K. (2026) · Molecular Therapy · doi:10.1016/j.ymthe.2026.09.022
The Adult Neurogenesis Theory of Alzheimer’s Disease Predicts Where Tauopathy Develops in the Brain
Abbate, C. (2026) · International Journal of Molecular Sciences · doi:10.3390/ijms27198776
Kozlov, I., Hung, Y., Roy, S., Goud, A. C., Kouřil, R., Wong, Y., & Das, V. (2026) · British Journal of Pharmacology · doi:10.1111/bph.70668
Shi, C. H., Zhu, B., Pina-Crespo, J., Chen, W. N., Vo, G. V., Huang, H., Yip, K. Y., & Huang, T. Y. (2026) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.64898/2026.10.15.759523
Metadata
- Authors
- Kaufman, S. K., Del Tredici, K., Thomas, T. L., Braak, H., & Diamond, M. I.
- Affiliations
- Washington University in St. Louis (US)
- The University of Texas Southwestern Medical Center (US)
- Universität Ulm (DE)
- Corresponding author
- Diamond, Marc I.
- Venue
- Acta Neuropathologica
- Published
- 2018-05-11
- Volume
- 136
- Issue
- 1
- Pages
- 57-67
- ISSN
- 0001-6322 (ISSN-L)
- 1432-0533
- PMC
- PMC6015098
- OpenAlex
- W2799729840
- Cited by
- 259
- References
- 46
- Citations by year
- 2026: 15 · 2025: 40 · 2024: 30 · 2023: 41 · 2022: 19 · 2021: 43 · 2020: 28 · 2019: 32 · 2018: 10
- FWCI
- 19.42
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Locations
- Acta Neuropathologica (publishedVersion, cc-by)
- bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion, cc-by-nc-nd)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Funders
- Rainwater Charitable Foundation (n/a)
- National Institute on Aging (R01AG048678)
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Alzheimer's disease research and treatments
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Keywords
- Alzheimer's disease, primary age-related tauopathy, locus coeruleus, neurofibrillary tangles, AT8 antibody, superior temporal gyrus, primary visual cortex, disease staging
- MeSH terms
- Adolescent, Adult, Aged, Aged, 80 and over, Alzheimer Disease, Animals, Female, Gene Expression Regulation, Humans, Locus Coeruleus, Male, Mice, Inbred C57BL, Microfilament Proteins, Middle Aged, Phosphorylation, Temporal Lobe, Visual Cortex, Neurofibrillary Tangles, tau Proteins, Mice, Knockout, Disease Progression, Entorhinal Cortex, Tauopathies, Mice, Young Adult, HEK293 Cells
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