Amyloid-β plaques enhance Alzheimer's brain tau-seeded pathologies by facilitating neuritic plaque tau aggregation
Open accessAbstract
Alzheimer's disease (AD) is characterized by extracellular amyloid-β (Aβ) plaques and intracellular tau inclusions. However, the exact mechanistic link between these two AD lesions remains enigmatic. Through injection of human AD-brain-derived pathological tau (AD-tau) into Aβ plaque-bearing mouse models that do not overexpress tau, we recapitulated the formation of three major types of AD-relevant tau pathologies: tau aggregates in dystrophic neurites surrounding Aβ plaques (NP tau), AD-like neurofibrillary tangles (NFTs) and neuropil threads (NTs). These distinct tau pathologies have different temporal onsets and functional consequences on neural activity and behavior. Notably, we found that Aβ plaques created a unique environment that facilitated the rapid amplification of proteopathic AD-tau seeds into large tau aggregates, initially appearing as NP tau, which was followed by the formation and spread of NFTs and NTs, likely through secondary seeding events. Our study provides insights into a new multistep mechanism underlying Aβ plaque-associated tau pathogenesis.
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Gradual accumulation of amyloid beta begins in the early stages of Alzheimer's disease and initiates synaptic loss, neuroinflammation, neurofibrillary tangle formation, and neuronal dysfunction.
“The gradual accumulation of amyloid-β (Aβ) begins in the early stages of Alzheimer’s disease (AD) and initiates a series of events resulting in synaptic loss, neuroinflammation, the formation of neurofibrillary tangles, and neuronal dysfunction [27, 30, 71].”
From Abnormal accumulation of extracellular vesicles in hippocampal dystrophic axons and regulation by the primary cilia in Alzheimer's disease (2023) · cites this paper as [27]
The Abstract describes Aβ plaque accumulation as an early event, and the Discussion proposes that plaques facilitate the formation and spread of neurofibrillary tangles, with later dysfunction. The Discussion also says plaques are not sufficient to initiate tau pathology without suitable tau seeds. Our copy does not establish the claimed sequence leading to synaptic loss and neuroinflammation. (LLM, conf=0.88)
Experimental — accuracy not yet measuredIt is well known that hyperphosphorylation of tau proteins leads to their accumulation into neurofibrillary tangles, which can potentially destabilize microtubules.
“It is well known that hyperphosphorylation of tau proteins leads to their accumulation into neurofibrillary tangles, which can potentially destabilize microtubules [27, 56].”
From Abnormal accumulation of extracellular vesicles in hippocampal dystrophic axons and regulation by the primary cilia in Alzheimer's disease (2023) · cites this paper as [27]
The Results section on NP tau aggregation reports that aggregated neuritic-plaque tau was hyperphosphorylated, and the paper describes subsequent formation of neurofibrillary tangles. It does not establish that hyperphosphorylation causes tangle formation. In the Results section on mislocalized tau, microtubule disruption is described as preceding tau disengagement in plaque-associated neurites, not as a potential consequence of tangles; no page numbers are available in our copy. (LLM, conf=0.86)
Experimental — accuracy not yet measuredGenetically decreasing TREM2 levels or altering its function in transgenic mice with amyloid plaque deposits injected with human AD brain-derived tau aggregates enhances tau propagation.
“Genetically decreasing TREM2 levels or altering its function in transgenic mice with amyloid plaque deposits injected with human AD brain-derived tau aggregates enhances tau propagation [19,30,31,32,39,40].”
From TREM2-Deficient Microglia Attenuate Tau Spreading In Vivo (2023) · cites this paper as [40]
The Results report enhanced tau pathology after injection of human AD-derived tau into plaque-bearing mice. They do not report genetically decreasing or altering TREM2; the gene reduced in this paper’s experiment was Mapt, and that reduction yielded less neuritic plaque tau. TREM2 appears in references cited for possible microglial involvement, not as a tested cause of enhanced tau propagation (page numbers unavailable). (LLM, conf=0.88)
Experimental — accuracy not yet measuredThe microenvironment in Aβ plaques plays a crucial role in Aβ-mediated neuroinflammation and tau pathogenesis in AD mouse models.
“Moreover, the microenvironment in Aβ plaques plays a crucial role in Aβ-mediated neuroinflammation and tau pathogenesis in AD mouse models [34, 53, 106].”
From Enhanced microglial dynamics and a paucity of tau seeding in the amyloid plaque microenvironment contribute to cognitive resilience in Alzheimer’s disease (2024) · cites this paper as [34]
The Discussion reports that Aβ plaques create an environment that facilitates seeded tau pathology in mouse models. It does not establish that this plaque microenvironment plays a crucial role in Aβ-mediated neuroinflammation; it mentions plaque-associated microglia only as a possible contributor to the link between plaques and tau pathology. Page numbers are unavailable in our copy. (LLM, conf=0.87)
Experimental — accuracy not yet measuredThis tau propagation could occur through axonal transmission to the neuronal soma and dendrites, ultimately leading to NFT formation.
“This tau propagation could occur through axonal transmission to the neuronal soma and dendrites, ultimately leading to NFT formation [34].”
From Enhanced microglial dynamics and a paucity of tau seeding in the amyloid plaque microenvironment contribute to cognitive resilience in Alzheimer’s disease (2024) · cites this paper as [34]
The Results section proposes that tau induced in dystrophic axons is transported retrogradely to neuronal somas, where it seeds NFT formation; the Discussion likewise suggests that neuritic-plaque tau may trigger NFTs in connected somas. Our copy does not specify transmission to dendrites, so that part of the claim is unsupported. No page number is available in the indexed passages. (LLM, conf=0.85)
Experimental — accuracy not yet measured
NFT formation and synaptic deterioration are not entirely dependent on Aβ plaque-mediated tau pathogenesis.
“However, NFT formation and synaptic deterioration are not entirely dependent on Aβ plaque–mediated tau pathogenesis [34]”
From Enhanced microglial dynamics and a paucity of tau seeding in the amyloid plaque microenvironment contribute to cognitive resilience in Alzheimer’s disease (2024) · cites this paper as [34]
The Results section on early seeding states that NFTs formed independently of Aβ plaques, supporting the NFT portion of the claim. The Results section on neural circuit activity reports impairment in mice with NFTs alone, but it does not establish synaptic deterioration specifically; no page numbers are available in our copy. (LLM, conf=0.83)
Experimental — accuracy not yet measuredPrior studies showed that either co-expressing APP and MAPT genes or using prion-like seeding paradigms led to exacerbated Aβ and tau pathologies.
“Previous studies have shown that either co-expressing APP and MAPT genes (3, 6, 23) or using prion-like seeding paradigms (4, 24, 25) led to exacerbated Aβ and tau pathologies.”
From Combinatorial model of amyloid β and tau reveals synergy between amyloid deposits and tangle formation (2022) · cites this paper as [25]
The Results section reports that injecting AD-derived tau into plaque-bearing mice induced neuritic-plaque tau pathology, supporting the prion-like seeding part of the claim. It does not show that seeding exacerbated Aβ pathology: the Aβ plaques were already present and facilitated tau aggregation. The APP/MAPT co-expression studies are cited alongside this paper, not findings of this study. (LLM, conf=0.86)
Experimental — accuracy not yet measuredIncreased neuritic dystrophy has been shown to facilitate tau spreading in tau pre-formed fibrils injection models.
“Since increased neuritic dystrophy has been shown to facilitate tau spreading in tau pre-formed fibrils injection models [49]”
From Astrocytic APOE3-Christchurch expression ameliorates brain amyloid-β pathology in 5xFAD mice (2026) · cites this paper as [49]
The Results section reports that plaque-associated dystrophic neurites facilitate aggregation of injected AD-derived tau and that the resulting aggregates may promote wider tau pathology through secondary seeding. But the same section reports no convincing tau pathology after injection of heparin-induced tau preformed fibrils (PFFs) in the mice tested. The claim therefore applies the AD-tau finding to a PFF-injection condition the paper does not support. (LLM, conf=0.88)
Experimental — accuracy not yet measuredTau aggregates initially appear in dystrophic neurites surrounding Aβ plaques (NP-tau) and subsequently spread.
“Previous studies have demonstrated that Aβ plaques create a unique environment that facilitates the rapid amplification of proteopathic tau seeds into large tau aggregates, which initially appear in dystrophic neurites surrounding Aβ plaques (NP-tau), followed by the formation and spread of tau aggregates [34].”
From Enhanced microglial dynamics and a paucity of tau seeding in the amyloid plaque microenvironment contribute to cognitive resilience in Alzheimer’s disease (2024) · cites this paper as [34]
It typically requires additional expression of human tau harboring mutations associated with primary tauopathy or seeding mutant human APP knock-in mouse brain with human AD brain-derived tau to develop tau pathology in mouse models.
“It typically requires additional expression of human tau harboring mutations associated with primary tauopathy (94–96) or seeding mutant human APP knock-in mouse brain with human AD brain-derived tau (97) to develop the tau pathology.”
From Modeling late-onset Alzheimer’s disease neuropathology via direct neuronal reprogramming (2024) · cites this paper as [97]
Aβ plaques create an environment that facilitates the rapid amplification of proteopathic tau seeds into large tau aggregates.
“Previous studies have demonstrated that Aβ plaques create a unique environment that facilitates the rapid amplification of proteopathic tau seeds into large tau aggregates, which initially appear in dystrophic neurites surrounding Aβ plaques (NP-tau), followed by the formation and spread of tau aggregates [34].”
From Enhanced microglial dynamics and a paucity of tau seeding in the amyloid plaque microenvironment contribute to cognitive resilience in Alzheimer’s disease (2024) · cites this paper as [34]
Highly phosphorylated tau species in dystrophic neurites surrounding Aβ plaques (NP-Tau) aggregate faster and spread more widely than tau in NFTs.
“These highly phosphorylated tau species in dystrophic neurites surrounding Aβ plaques (NP-Tau) aggregate faster and spread more widely than tau in NFTs [34].”
From Enhanced microglial dynamics and a paucity of tau seeding in the amyloid plaque microenvironment contribute to cognitive resilience in Alzheimer’s disease (2024) · cites this paper as [34]
When human AD-derived tau was injected into a plaque-bearing 5xFAD mouse model, Aβ plaques facilitated the conversion and seeding of pathological tau in dystrophic neurites during the early stages of pathology.
“Furthermore, He et al. reported that when human AD-derived tau was injected into a plaque-bearing 5xFAD mouse model, Aβ plaques facilitated the conversion and seeding of pathological tau in dystrophic neurites during the early stages of pathology.”
From Enhanced microglial dynamics and a paucity of tau seeding in the amyloid plaque microenvironment contribute to cognitive resilience in Alzheimer’s disease (2024) · cites this paper as [34]
Aβ accumulation stimulates tau phosphorylation and fibrillary tangle formation, leading to neurodegeneration.
“Growing evidence indicates that Aβ accumulation stimulates tau phosphorylation and fibrillary tangle formation, leading to the process of neurodegeneration.112–114”
From Amyloid β-based therapy for Alzheimer’s disease: Challenges, successes and future (2023) · cites this paper as [114]
The first tau deposits initiated by Aβ may occur in dystrophic neurites surrounding the Aβ plaques, with the formation of widespread tangle pathology coming later, potentially spreading through functionally connected neurons.
“The first tau deposits that are initiated by Aβ may occur in dystrophic neurites surrounding the Aβ plaques, with the formation of widespread tangle pathology coming later (29), potentially spreading through functionally connected neurons.”
From Aβ deposition is associated with increases in soluble and phosphorylated tau that precede a positive tau PET in Alzheimer's disease (2020) · cites this paper as [29]
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Cites
Amyloid 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 · see citing works
Alzheimer's disease: the amyloid cascade hypothesis
Hardy, J. A., & Higgins, G. A. (1992) · Science · doi:10.1126/science.1566067 · Cited by 7,484 · see citing works
Oakley, H., Cole, S. L., Logan, S., Maus, E., Shao, P., Craft, J., Guillozet-Bongaarts, A., Ohno, M., Disterhoft, J., Van Eldik, L., et al. (2006) · The Journal of Neuroscience · doi:10.1523/jneurosci.1202-06.2006 · Cited by 3,530 · see citing works
Hyman, 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 · see citing works
Self-citationMontine, T. J., Phelps, C. H., Beach, T. G., Bigio, E. H., Cairns, N. J., Dickson, D. W., Duyckaerts, C., Frosch, M. P., Masliah, E., Mirra, S. S., et al. (2012) · Acta Neuropathologica · doi:10.1007/s00401-011-0910-3 · Cited by 2,992 · see citing works
Self-citationStages 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 · see citing works
Transmission and spreading of tauopathy in transgenic mouse brain
Clavaguera, F., Bolmont, T., Crowther, R. A., Abramowski, D., Frank, S., Probst, A., Fraser, G., Stalder, A. K., Beibel, M., Staufenbiel, M., et al. (2009) · Nature Cell Biology · doi:10.1038/ncb1901 · Cited by 1,803 · see citing works
Enhanced neurofibrillary degeneration in transgenic mice expressing mutant tau and APP
Lewis, J., Dickson, D. W., Lin, W.-L., Chisholm, L., Corral, A., Jones, G., Yen, S.-H., Sahara, N., Skipper, L., Yager, D., et al. (2001) · Science · doi:10.1126/science.1058189 · Cited by 1,611 · see citing works
Formation of Neurofibrillary Tangles in P301L Tau Transgenic Mice Induced by Aβ42 Fibrils
Götz, J., Chen, F., van Dorpe, J., & Nitsch, R. M. (2001) · Science · doi:10.1126/science.1062097 · Cited by 1,526 · see citing works
Neuronal loss correlates with but exceeds neurofibrillary tangles in Alzheimer's disease
Gómez‐Isla, T., Hollister, R., West, H., Mui, S., Growdon, J. H., Petersen, R. C., Parisi, J. E., & Hyman, B. T. (1997) · Annals of Neurology · doi:10.1002/ana.410410106 · Cited by 1,489 · see citing works
Primary age-related tauopathy (PART): a common pathology associated with human aging
Crary, J. F., Trojanowski, J. Q., Schneider, J. A., Abisambra, J. F., Abner, E. L., Alafuzoff, I., Arnold, S. E., Attems, J., Beach, T. G., Bigio, E. H., et al. (2014) · Acta Neuropathologica · doi:10.1007/s00401-014-1349-0 · Cited by 1,467 · see citing works
Self-citationRegional dissociations within the hippocampus-memory and anxiety
Bannerman, D. M., Rawlins, J. N. P., McHugh, S. B., Deacon, R. M. J., Yee, B. K., Bast, T., Zhang, W.-N., Pothuizen, H. H. J., & Feldon, J. (2004) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2004.03.004 · Cited by 1,462 · see citing works
Single App knock-in mouse models of Alzheimer’s disease
Saito, T., Matsuba, Y., Mihira, N., Takano, J., Nilsson, P., Itohara, S., Iwata, N., & Saido, T. C. (2014) · Nature Neuroscience · doi:10.1038/nn.3697 · Cited by 1,447 · see citing works
PET Imaging of Tau Deposition in the Aging Human Brain
Schöll, M., Lockhart, S. N., Schonhaut, D. R., O’Neil, J. P., Janabi, M., Ossenkoppele, R., Baker, S. L., Vogel, J. W., Faria, J., Schwimmer, H. D., et al. (2016) · Neuron · doi:10.1016/j.neuron.2016.01.028 · Cited by 1,214 · see citing works
Exogenous Induction of Cerebral ß-Amyloidogenesis Is Governed by Agent and Host
Meyer-Luehmann, M., Coomaraswamy, J., Bolmont, T., Kaeser, S., Schaefer, C., Kilger, E., Neuenschwander, A., Abramowski, D., Frey, P., Jaton, A. L., et al. (2006) · Science · doi:10.1126/science.1131864 · Cited by 971 · see citing works
TREM2-mediated early microglial response limits diffusion and toxicity of amyloid plaques
Wang, Y., Ulland, T. K., Ulrich, J. D., Song, W., Tzaferis, J. A., Hole, J. T., Yuan, P., Mahan, T. E., Shi, Y., Gilfillan, S., et al. (2016) · Journal of Experimental Medicine · doi:10.1084/jem.20151948 · Cited by 840 · see citing works
Yuan, P., Condello, C., Keene, C. D., Wang, Y., Bird, T. D., Paul, S. M., Luo, W., Colonna, M., Baddeley, D., & Grutzendler, J. (2016) · Neuron · doi:10.1016/j.neuron.2016.05.003 · Cited by 817 · see citing works
Tau and Aβ imaging, CSF measures, and cognition in Alzheimer’s disease
Brier, M. R., Gordon, B., Friedrichsen, K., McCarthy, J., Stern, A., Christensen, J., Owen, C., Aldea, P., Su, Y., Hassenstab, J., et al. (2016) · Science Translational Medicine · doi:10.1126/scitranslmed.aaf2362 · Cited by 734 · see citing works
Iba, M., Guo, J. L., McBride, J. D., Zhang, B., Trojanowski, J. Q., & Lee, V. M.-Y. (2013) · The Journal of Neuroscience · doi:10.1523/jneurosci.2642-12.2013 · Cited by 664 · see citing works
Self-citationNeuropathology and Cognitive Impairment in Alzheimer Disease: A Complex but Coherent Relationship
Nelson, P. T., Braak, H., & Markesbery, W. R. (2009) · Journal of Neuropathology & Experimental Neurology · doi:10.1097/nen.0b013e3181919a48 · Cited by 643 · see citing works
Seeding of Normal Tau by Pathological Tau Conformers Drives Pathogenesis of Alzheimer-like Tangles
Guo, J. L., & Lee, V. M.-Y. (2011) · Journal of Biological Chemistry · doi:10.1074/jbc.m110.209296 · Cited by 636 · see citing works
Self-citationPeripherally Applied Aβ-Containing Inoculates Induce Cerebral β-Amyloidosis
Eisele, Y. S., Obermüller, U., Heilbronner, G., Baumann, F., Kaeser, S. A., Wolburg, H., Walker, L. C., Staufenbiel, M., Heikenwalder, M., & Jucker, M. (2010) · Science · doi:10.1126/science.1194516 · Cited by 568 · see citing works
Bennett, D. A., Schneider, J. A., Wilson, R. S., Bienias, J. L., & Arnold, S. E. (2004) · Archives of Neurology · doi:10.1001/archneur.61.3.378 · Cited by 526 · see citing works
Mann, D. M. A., & Esiri, M. M. (1989) · Journal of the Neurological Sciences · doi:10.1016/0022-510x(89)90019-1 · Cited by 471 · see citing works
Guo, J. L., Narasimhan, S., Changolkar, L., He, Z., Stieber, A., Zhang, B., Gathagan, R. J., Iba, M., McBride, J. D., Trojanowski, J. Q., et al. (2016) · Journal of Experimental Medicine · doi:10.1084/jem.20160833 · Cited by 440 · see citing works
Self-citationSchwarz, A. J., Yu, P., Miller, B. B., Shcherbinin, S., Dickson, J., Navitsky, M., Joshi, A. D., Devous, M. D., & Mintun, M. S. (2016) · Brain · doi:10.1093/brain/aww023 · Cited by 425 · see citing works
Almeida, C. G., Takahashi, R. H., & Gouras, G. K. (2006) · The Journal of Neuroscience · doi:10.1523/jneurosci.5078-05.2006 · Cited by 316 · see citing works
Wang, L. Y., Benzinger, T. L. S., Su, Y., Christensen, J. J., Friedrichsen, K. A., Aldea, P., McConathy, J., Cairns, N. J., Fagan, A. M., Morris, J. C., et al. (2016) · JAMA Neurology · doi:10.1001/jamaneurol.2016.2078 · Cited by 295 · see citing works
Sadleir, K. R., Kandalepas, P. C., Buggia-Prévot, V., Nicholson, D. A., Thinakaran, G., & Vassar, R. (2016) · Acta Neuropathologica · doi:10.1007/s00401-016-1558-9 · Cited by 294 · see citing works
Bolmont, T., Clavaguera, F., Meyer-Luehmann, M., Herzig, M. C., Radde, R., Staufenbiel, M., Lewis, J., Hutton, M., Tolnay, M., & Jucker, M. (2007) · The American Journal of Pathology · doi:10.2353/ajpath.2007.070403 · Cited by 281 · see citing works
Enhanced tau aggregation in the presence of Amyloid β
Bennett, R. E., DeVos, S. L., Dujardin, S., Corjuc, B., Gor, R., Gonzalez, J., Roe, A. D., Frosch, M. P., Pitstick, R., Carlson, G. A., et al. (2017) · The American Journal of Pathology · doi:10.1016/j.ajpath.2017.03.011 · Cited by 245 · see citing works
Behavioral characterization of the Tg2576 transgenic model of Alzheimer's disease through 19 months
King, D. L., & Arendash, G. W. (2002) · Physiology & Behavior · doi:10.1016/s0031-9384(02)00639-x · Cited by 240 · see citing works
Soluble Aβ Seeds Are Potent Inducers of Cerebral β-Amyloid Deposition
Langer, F., Eisele, Y. S., Fritschi, S. K., Staufenbiel, M., Walker, L. C., & Jucker, M. (2011) · The Journal of Neuroscience · doi:10.1523/jneurosci.3088-11.2011 · Cited by 237 · see citing works
Amyloid accelerates tau propagation and toxicity in a model of early Alzheimer’s disease
Pooler, A. M., Polydoro, M., Maury, E. A., Nicholls, S. B., Reddy, S. M., Wegmann, S., William, C., Saqran, L., Cagsal-Getkin, O., Pitstick, R., et al. (2015) · Acta Neuropathologica Communications · doi:10.1186/s40478-015-0199-x · Cited by 236 · see citing works
Hurtado, D. E., Molina-Porcel, L., Iba, M., Aboagye, A. K., Paul, S. M., Trojanowski, J. Q., & Lee, V. M.-Y. (2010) · The American Journal of Pathology · doi:10.2353/ajpath.2010.100346 · Cited by 222 · see citing works
Self-citationCharacterization of Two VQIXXK Motifs for Tau Fibrillization in Vitro
Li, W., & Lee, V. M. ‐. (2006) · Biochemistry · doi:10.1021/bi061422+ · Cited by 197 · see citing works
Self-citationIn Vivo Tau, Amyloid, and Gray Matter Profiles in the Aging Brain
Sepulcre, J., Schultz, A. P., Sabuncu, M. R., Gómez‐Isla, T., Chhatwal, J. P., Becker, A., Sperling, R. A., & Johnson, K. A. (2016) · Journal of Neuroscience · doi:10.1523/jneurosci.0639-16.2016 · Cited by 175 · see citing works
Extracellular amyloid formation and associated pathology in neural grafts
Meyer‐Luehmann, M., Stalder, M., Herzig, M. C., Kaeser, S. A., Kohler, E., Pfeifer, M., Boncristiano, S., Mathews, P. M., Mercken, M. H., Abramowski, D., et al. (2003) · Nature Neuroscience · doi:10.1038/nn1022 · Cited by 133 · see citing works
Exogenous seeding of cerebral β‐amyloid deposition in βAPP‐transgenic rats
Rosen, R. F., Fritz, J. J., Dooyema, J. M., Cintron, A. F., Hamaguchi, T., Lah, J. J., LeVine, H., Jucker, M., & Walker, L. C. (2011) · Journal of Neurochemistry · doi:10.1111/j.1471-4159.2011.07551.x · Cited by 121 · see citing works
Multisite assessment of NIA‐AA guidelines for the neuropathologic evaluation of Alzheimer's disease
Montine, T. J., Monsell, S. E., Beach, T. G., Bigio, E. H., Bu, Y., Cairns, N. J., Frosch, M., Henriksen, J., Kofler, J., Kukull, W. A., et al. (2016) · Alzheimer's & Dementia · doi:10.1016/j.jalz.2015.07.492 · Cited by 113 · see citing works
Self-citationLee, E. B., Skovronsky, D., Abtahian, F., Doms, R. W., & Lee, V. M. ‐. (2003) · Journal of Biological Chemistry · doi:10.1074/jbc.m210105200 · Cited by 78 · see citing works
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Alzheimer Disease: An Update on Pathobiology and Treatment Strategies
Long, J. M., & Holtzman, D. M. (2019) · Cell · doi:10.1016/j.cell.2019.09.001 · Cited by 3,204 · see citing works
The Amyloid-β Pathway in Alzheimer’s Disease
Hampel, H., Hardy, J., Blennow, K., Chen, C., Perry, G., Kim, S. H., Villemagne, V. L., Aisen, P., Vendruscolo, M., Iwatsubo, T., et al. (2021) · Molecular Psychiatry · doi:10.1038/s41380-021-01249-0 · Cited by 1,952 · see citing works
Synergy between amyloid-β and tau in Alzheimer’s disease
Busche, M. A., & Hyman, B. T. (2020) · Nature Neuroscience · doi:10.1038/s41593-020-0687-6 · Cited by 1,242 · see citing works
Protein misfolding, aggregation, and conformational strains in neurodegenerative diseases
Soto, C., & Pritzkow, S. (2018) · Nature Neuroscience · doi:10.1038/s41593-018-0235-9 · Cited by 1,180 · see citing works
Wang, X., Sun, G., Feng, T., Zhang, J., Huang, X., Wang, T., Xie, Z., Chu, X., Yang, J., Wang, H., et al. (2019) · Cell Research · doi:10.1038/s41422-019-0216-x · Cited by 1,144 · see citing works
Amyloid β-based therapy for Alzheimer’s disease: Challenges, successes and future
Zhang, Y., Chen, H., Li, R., Sterling, K., & Song, W. (2023) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-023-01484-7 · Cited by 988 · see citing works
A critical appraisal of amyloid-β-targeting therapies for Alzheimer disease
Panza, F., Lozupone, M., Logroscino, G., & Imbimbo, B. P. (2019) · Nature Reviews Neurology · doi:10.1038/s41582-018-0116-6 · Cited by 965 · see citing works
Reconsideration of Amyloid Hypothesis and Tau Hypothesis in Alzheimer's Disease
Kametani, F., & Hasegawa, M. (2018) · Frontiers in Neuroscience · doi:10.3389/fnins.2018.00025 · Cited by 836 · see citing works
the Dominantly Inherited Alzheimer Network, Barthélemy, N. R., Li, Y., Joseph-Mathurin, N., Gordon, B. A., Hassenstab, J., Benzinger, T. L. S., Buckles, V., Fagan, A. M., Perrin, R. J., et al. (2020) · Nature Medicine · doi:10.1038/s41591-020-0781-z · Cited by 651 · see citing works
Protein transmission in neurodegenerative disease
Peng, C., Trojanowski, J. Q., & Lee, V. M.-Y. (2020) · Nature Reviews Neurology · doi:10.1038/s41582-020-0333-7 · Cited by 625 · see citing works
Self-citationAnimal models of neurodegenerative diseases
Dawson, T. M., Golde, T. E., & Lagier-Tourenne, C. (2018) · Nature Neuroscience · doi:10.1038/s41593-018-0236-8 · Cited by 576 · see citing works
Wang, C., & Holtzman, D. M. (2019) · Neuropsychopharmacology · doi:10.1038/s41386-019-0478-5 · Cited by 589 · see citing works
Spread of pathological tau proteins through communicating neurons in human Alzheimer’s disease
Vogel, J. W., Iturria‐Medina, Y., Strandberg, O. T., Smith, R. A., Levitis, E., Evans, A. C., Hansson, O., Initiative, A. D. N., Weiner, M. W., Aisen, P., et al. (2020) · Nature Communications · doi:10.1038/s41467-020-15701-2 · Cited by 521 · see citing works
Self-citationCurrent state of Alzheimer’s fluid biomarkers
Molinuevo, J. L., Ayton, S., Batrla, R., Bednar, M. M., Bittner, T., Cummings, J., Fagan, A. M., Hampel, H., Mielke, M. M., Mikulskis, A., et al. (2018) · Acta Neuropathologica · doi:10.1007/s00401-018-1932-x · Cited by 518 · see citing works
Self-citationTau molecular diversity contributes to clinical heterogeneity in Alzheimer’s disease
Dujardin, S., Commins, C., Lathuiliere, A., Beerepoot, P., Fernandes, A. R., Kamath, T. V., De Los Santos, M. B., Klickstein, N., Corjuc, D. L., Corjuc, B. T., et al. (2020) · Nature Medicine · doi:10.1038/s41591-020-0938-9 · Cited by 438 · see citing works
Propagation and spread of pathogenic protein assemblies in neurodegenerative diseases
Jucker, M., & Walker, L. C. (2018) · Nature Neuroscience · doi:10.1038/s41593-018-0238-6 · Cited by 450 · see citing works
Alzheimer’s disease: insights into pathology, molecular mechanisms, and therapy
Zheng, Q., & Wang, X. (2024) · Protein & Cell · doi:10.1093/procel/pwae026 · Cited by 454 · see citing works
Tau impairs neural circuits, dominating amyloid-β effects, in Alzheimer models in vivo
Busche, M. A., Wegmann, S., Dujardin, S., Commins, C., Schiantarelli, J., Klickstein, N., Kamath, T. V., Carlson, G. A., Nelken, I., & Hyman, B. T. (2019) · Nature Neuroscience · doi:10.1038/s41593-018-0289-8 · Cited by 413 · see citing works
Rodent models for Alzheimer disease
Götz, J., Bodea, L., & Goedert, M. (2018) · Nature reviews. Neuroscience · doi:10.1038/s41583-018-0054-8 · Cited by 397 · see citing works
Neuropathology of Alzheimer's Disease
Trejo‐Lopez, J. A., Yachnis, A. T., & Prokop, S. (2021) · Neurotherapeutics · doi:10.1007/s13311-021-01146-y · Cited by 398 · see citing works
Emerging diagnostics and therapeutics for Alzheimer disease
Self, W. K., & Holtzman, D. M. (2023) · Nature Medicine · doi:10.1038/s41591-023-02505-2 · Cited by 381 · see citing works
The complexity of tau in Alzheimer’s disease
Naseri, N. N., Wang, H., Guo, J. D., Sharma, M., & Luo, W. (2019) · Neuroscience Letters · doi:10.1016/j.neulet.2019.04.022 · Cited by 374 · see citing works
Self-citationMattsson-Carlgren, N., Andersson, E., Janelidze, S., Ossenkoppele, R., Insel, P., Strandberg, O., Zetterberg, H., Rosen, H. J., Rabinovici, G., Chai, X., et al. (2020) · Science Advances · doi:10.1126/sciadv.aaz2387 · Cited by 359 · see citing works
Cerebral blood flow decrease as an early pathological mechanism in Alzheimer's disease
Korte, N., Nortley, R., & Attwell, D. (2020) · Acta Neuropathologica · doi:10.1007/s00401-020-02215-w · Cited by 343 · see citing works
TREM2 function impedes tau seeding in neuritic plaques
Leyns, C. E. G., Gratuze, M., Narasimhan, S., Jain, N., Koscal, L. J., Jiang, H., Manis, M., Colonna, M., Lee, V. M. Y., Ulrich, J. D., et al. (2019) · Nature Neuroscience · doi:10.1038/s41593-019-0433-0 · Cited by 332 · see citing works
Self-citationAmyloid-beta peptide and tau protein crosstalk in Alzheimer’s disease
Villegas, S., Roda, A., Serra-Mir, G., Montoliu-Gaya, L., & Tiessler, L. (2022) · Neural Regeneration Research · doi:10.4103/1673-5374.332127 · Cited by 306 · see citing works
Emerging roles of innate and adaptive immunity in Alzheimer’s disease
Chen, X., & Holtzman, D. M. (2022) · Immunity · doi:10.1016/j.immuni.2022.10.016 · Cited by 297 · see citing works
Trem2 restrains the enhancement of tau accumulation and neurodegeneration by β-amyloid pathology
Lee, S.-H., Meilandt, W. J., Xie, L., Gandham, V. D., Ngu, H., Barck, K. H., Rezzonico, M. G., Imperio, J., Lalehzadeh, G., Huntley, M. A., et al. (2021) · Neuron · doi:10.1016/j.neuron.2021.02.010 · Cited by 300 · see citing works
The AHEAD 3‐45 Study: Design of a prevention trial for Alzheimer's disease
Rafii, M. S., Sperling, R. A., Donohue, M. C., Zhou, J., Roberts, C., Irizarry, M. C., Dhadda, S., Sethuraman, G., Kramer, L. D., Swanson, C. J., et al. (2023) · Alzheimer's & Dementia · doi:10.1002/alz.12748 · Cited by 291 · see citing works
Therriault, J., Vermeiren, M. R., Servaes, S., Tissot, C., Ashton, N. J., Benedet, A. L., Karikari, T. K., Lantero‐Rodriguez, J., Brum, W. S., Lussier, F. Z., et al. (2022) · JAMA Neurology · doi:10.1001/jamaneurol.2022.4485 · Cited by 268 · see citing works
Longitudinal tau accumulation and atrophy in aging and alzheimer disease
Harrison, T. M., Joie, R. L., Maaß, A., Baker, S. L., Swinnerton, K. N., Fenton, L. E., Mellinger, T. J., Edwards, L., Pham, J. Q., Miller, B. L., et al. (2018) · Annals of Neurology · doi:10.1002/ana.25406 · Cited by 262 · see citing works
The human connectome in Alzheimer disease — relationship to biomarkers and genetics
Yu, M., Sporns, O., & Saykin, A. J. (2021) · Nature Reviews Neurology · doi:10.1038/s41582-021-00529-1 · Cited by 265 · see citing works
Mechanisms of Cell-to-Cell Transmission of Pathological Tau: A Review
Gibbons, G. S., Lee, V. M. Y., & Trojanowski, J. Q. (2019) · JAMA Neurology · doi:10.1001/jamaneurol.2018.2505 · Cited by 257 · see citing works
Self-citationSaito, T., Mihira, N., Matsuba, Y., Sasaguri, H., Hashimoto, S., Narasimhan, S., Zhang, B., Murayama, S., Higuchi, M., Lee, V. M. Y., et al. (2019) · Journal of Biological Chemistry · doi:10.1074/jbc.ra119.009487 · Cited by 248 · see citing works
Self-citationBassil, F., Brown, H. J., Pattabhiraman, S., Iwasyk, J. E., Maghames, C. M., Meymand, E. S., Cox, T. O., Riddle, D. M., Zhang, B., Trojanowski, J. Q., et al. (2019) · Neuron · doi:10.1016/j.neuron.2019.10.010 · Cited by 243 · see citing works
Self-citationClayton, K., Delpech, J. C., Herron, S., Iwahara, N., Ericsson, M., Saito, T., Saido, T. C., Ikezu, S., & Ikezu, T. (2021) · Molecular Neurodegeneration · doi:10.1186/s13024-021-00440-9 · Cited by 245 · see citing works
Protein acylation: mechanisms, biological functions and therapeutic targets
Shang, S., Liu, J., & Hua, F. (2022) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-022-01245-y · Cited by 247 · see citing works
The Role of Microglia and the Nlrp3 Inflammasome in Alzheimer's Disease
Hanslik, K. L., & Ulland, T. K. (2020) · Frontiers in Neurology · doi:10.3389/fneur.2020.570711 · Cited by 236 · see citing works
Li, P., Marshall, L., Oh, G., Jakubowski, J. L., Groot, D., He, Y., Wang, T., Petronis, A., & Labrie, V. (2019) · Nature Communications · doi:10.1038/s41467-019-10101-7 · Cited by 234 · see citing works
MEG3 activates necroptosis in human neuron xenografts modeling Alzheimer’s disease
Balusu, S., Horré, K., Thrupp, N., Craessaerts, K., Snellinx, A., Serneels, L., T’Syen, D., Chrysidou, I., Arranz, A. M., Sierksma, A. S. R., et al. (2023) · Science · doi:10.1126/science.abp9556 · Cited by 234 · see citing works
Dural lymphatics regulate clearance of extracellular tau from the CNS
Patel, T. K., Habimana-Griffin, L., Gao, X., Xu, B. J., Achilefu, S., Alitalo, K. K., McKee, C. A., Sheehan, P. W., Musiek, E. S., Xiong, C., et al. (2019) · Molecular Neurodegeneration · doi:10.1186/s13024-019-0312-x · Cited by 215 · see citing works
Activated microglia mitigate Aβ-associated tau seeding and spreading
Gratuze, M., Chen, Y., Parhizkar, S., Jain, N., Strickland, M. R., Serrano, J. R., Colonna, M., Ulrich, J. D., & Holtzman, D. M. (2021) · Journal of Experimental Medicine · doi:10.1084/jem.20210542 · Cited by 215 · see citing works
Mouse Models of Alzheimer’s Disease
Yokoyama, M., Kobayashi, H., Tatsumi, L., & Tomita, T. (2022) · Frontiers in Molecular Neuroscience · doi:10.3389/fnmol.2022.912995 · Cited by 213 · see citing works
Meilandt, W. J., Ngu, H., Gogineni, A., Lalehzadeh, G., Lee, S.-H., Srinivasan, K., Imperio, J., Wu, T., Weber, M., Kruse, A. J., et al. (2020) · The Journal of Neuroscience · doi:10.1523/jneurosci.1871-19.2019 · Cited by 210 · see citing works
Amyloid-β and Tau at the Crossroads of Alzheimer’s Disease
Gallardo, G., & Holtzman, D. M. (2019) · Advances in experimental medicine and biology · doi:10.1007/978-981-32-9358-8_16 · Cited by 201 · see citing works
Regional Aβ-tau interactions promote onset and acceleration of Alzheimer’s disease tau spreading
Lee, W. J., Brown, J. A., Kim, H. R., Joie, R. L., Cho, H., Lyoo, C. H., Rabinovici, G. D., Seong, J., & Seeley, W. W. (2022) · Neuron · doi:10.1016/j.neuron.2022.03.034 · Cited by 193 · see citing works
Self-citationUltrasound-Based Micro-/Nanosystems for Biomedical Applications
Huang, H. F., Zheng, Y., Chang, M., Song, J., Xia, L., Wu, C., Jia, W., Ren, H., Feng, W., & Chen, Y. (2024) · Chemical Reviews · doi:10.1021/acs.chemrev.4c00009 · Cited by 186 · see citing works
Amyloid assembly and disassembly
Chuang, E., Hori, A. M., Hesketh, C. D., & Shorter, J. (2018) · Journal of Cell Science · doi:10.1242/jcs.189928 · Cited by 182 · see citing works
Gordon, B. A., Blazey, T. M., Christensen, J., Dincer, A., Flores, S., Keefe, S., Chen, C., Su, Y., McDade, E. M., Wang, G., et al. (2019) · Brain · doi:10.1093/brain/awz019 · Cited by 180 · see citing works
Park, J., Han, S.-H., Yi, D., Byun, M. S., Lee, J. H., Jang, S. S., Ko, K., Jeon, S. Y., Lee, Y., Kim, Y. K., et al. (2018) · Brain · doi:10.1093/brain/awy347 · Cited by 178 · see citing works
Mechanisms of Pathogenic Tau and Aβ Protein Spreading in Alzheimer’s Disease
d’Errico, P., & Meyer‐Luehmann, M. (2020) · Frontiers in Aging Neuroscience · doi:10.3389/fnagi.2020.00265 · Cited by 182 · see citing works
Transmission of tauopathy strains is independent of their isoform composition
He, Z., McBride, J. D., Xu, H. W., Changolkar, L. N., Kim, S., Zhang, B., Narasimhan, S., Gibbons, G. S., Guo, J., Kozak, M., et al. (2020) · Nature Communications · doi:10.1038/s41467-019-13787-x · Cited by 177 · see citing works
Self-citationThe Role of Glymphatic System in Alzheimer’s and Parkinson’s Disease Pathogenesis
Buccellato, F. R., D’Anca, M., Serpente, M., Arighi, A., & Galimberti, D. (2022) · Biomedicines · doi:10.3390/biomedicines10092261 · Cited by 184 · see citing works
Lau, V. Z., Ramer, L. M., & Tremblay, M. (2023) · Nature Communications · doi:10.1038/s41467-023-37304-3 · Cited by 168 · see citing works
The Toxicity and Polymorphism of β-Amyloid Oligomers
Huang, Y., & Liu, R. (2020) · International Journal of Molecular Sciences · doi:10.3390/ijms21124477 · Cited by 168 · see citing works
Limorenko, G., & Lashuel, H. A. (2021) · Chemical Society Reviews · doi:10.1039/d1cs00127b · Cited by 162 · see citing works
Apoptosis and its therapeutic implications in neurodegenerative diseases
Erekat, N. S. (2021) · Clinical Anatomy · doi:10.1002/ca.23792 · Cited by 163 · see citing works
Non-Alzheimer’s contributions to dementia and cognitive resilience in The 90+ Study
Robinson, J. L., Corrada, M. M., Kovács, G. G., Dominique, M. A., Caswell, C., Xie, S. X., Lee, V. M. ‐., Kawas, C. H., & Trojanowski, J. Q. (2018) · Acta Neuropathologica · doi:10.1007/s00401-018-1872-5 · Cited by 163 · see citing works
Self-citationPLD3 affects axonal spheroids and network defects in Alzheimer’s disease
Yuan, P., Zhang, M., Tong, L., Morse, T. M., McDougal, R. A., Ding, H., Chan, D., Cai, Y., & Grutzendler, J. (2022) · Nature · doi:10.1038/s41586-022-05491-6 · Cited by 155 · see citing works
Invited Review: The role of prion‐like mechanisms in neurodegenerative diseases
Jaunmuktane, Z., & Brandner, S. (2019) · Neuropathology and Applied Neurobiology · doi:10.1111/nan.12592 · Cited by 147 · see citing works
Liver Dysfunction as a Novel Player in Alzheimer’s Progression: Looking Outside the Brain
Estrada, L. D., Ahumada, P., Cabrera, D., & Arab, J. P. (2019) · Frontiers in Aging Neuroscience · doi:10.3389/fnagi.2019.00174 · Cited by 144 · see citing works
Chronic TREM2 activation exacerbates Aβ-associated tau seeding and spreading
Jain, N., Lewis, C. A., Ulrich, J. D., & Holtzman, D. M. (2023) · Journal of Experimental Medicine · doi:10.1084/jem.20220654 · Cited by 146 · see citing works
Zhao, P., Xu, Y., Jiang, L., Fan, X., Li, L., Li, X., Arase, H., Zhao, Y., Cao, W., Zheng, H., et al. (2022) · Science Translational Medicine · doi:10.1126/scitranslmed.abq0095 · Cited by 141 · see citing works
Cell-to-Cell Transmission of Tau and α-Synuclein
Uemura, N., Uemura, M. T., Luk, K. C., Lee, V. M. ‐., & Trojanowski, J. Q. (2020) · Trends in Molecular Medicine · doi:10.1016/j.molmed.2020.03.012 · Cited by 141 · see citing works
Self-citationWould Colloidal Gold Nanocarriers Present An Effective Diagnosis Or Treatment For Ischemic Stroke?
Amani, H., Mostafavi, E., Alebouyeh, M. R., Arzaghi, H., Akbarzadeh, A., Pazoki–Toroudi, H., & Webster, T. J. (2019) · International Journal of Nanomedicine · doi:10.2147/ijn.s210035 · Cited by 142 · see citing works
Current and emerging avenues for Alzheimer's disease drug targets
Loera‐Valencia, R., Cedazo-Mı́nguez, Á., Kenigsberg, P.-A., Page, G., Duarte, A. I., Giusti, P., Zusso, M., Robert, P. H., Frisoni, G. B., Cattaneo, A., et al. (2019) · Journal of Internal Medicine · doi:10.1111/joim.12959 · Cited by 139 · see citing works
Autosomal dominant VCP hypomorph mutation impairs disaggregation of PHF-tau
Darwich, N. F., Phan, J. M., Kim, B., Suh, E. R., Papatriantafyllou, J. D., Changolkar, L. N., Nguyen, A. T., O’Rourke, C. M., He, Z., Porta, S., et al. (2020) · Science · doi:10.1126/science.aay8826 · Cited by 141 · see citing works
Self-citationMicroglia in Alzheimer's Disease: Risk Factors and Inflammation
Katsumoto, A., Takeuchi, H., Takahashi, K., & Tanaka, F. (2018) · Frontiers in Neurology · doi:10.3389/fneur.2018.00978 · Cited by 138 · see citing works
Tau pathology in neurodegenerative disease: disease mechanisms and therapeutic avenues
Samudra, N. P., Lane‐Donovan, C., VandeVrede, L. A., & Boxer, A. L. (2023) · Journal of Clinical Investigation · doi:10.1172/jci168553 · Cited by 135 · see citing works
Genome-wide meta-analysis for Alzheimer’s disease cerebrospinal fluid biomarkers
Jansen, I. E., van der Lee, S. J., Gomez-Fonseca, D., de Rojas, I., Dalmasso, M. C., Grenier-Boley, B., Zettergren, A., Mishra, A., Ali, M., Andrade, V., et al. (2022) · Acta Neuropathologica · doi:10.1007/s00401-022-02454-z · Cited by 132 · see citing works
Aβ and tau prion-like activities decline with longevity in the Alzheimer’s disease human brain
Aoyagi, A., Condello, C., Stöhr, J., Yue, W., Rivera, B. M., Lee, J. C., Woerman, A. L., Halliday, G. M., van Duinen, S. G., Ingelsson, M., et al. (2019) · Science Translational Medicine · doi:10.1126/scitranslmed.aat8462 · Cited by 130 · see citing works
β-amyloid redirects norepinephrine signaling to activate the pathogenic GSK3β/tau cascade
Zhang, F., Gannon, M., Chen, Y., Yan, S., Zhang, S., Feng, W., Tao, J., Sha, B., Liu, Z., Saito, T., et al. (2020) · Science Translational Medicine · doi:10.1126/scitranslmed.aay6931 · Cited by 133 · see citing works
Cai, L., Yang, C., Jia, W., Liu, Y., Xie, R., Lei, T., Yang, Z., He, X., Tong, R., & Gao, H. (2020) · Advanced Functional Materials · doi:10.1002/adfm.201909999 · Cited by 132 · see citing works
(2022) · doi:10.1038/s41467-022-34129-4 · Cited by 128 · see citing works
Self-citationWang, H., Yang, F., Zhang, S., Xin, R., & Sun, Y. (2021) · npj Parkinson s Disease · doi:10.1038/s41531-021-00213-7 · Cited by 130 · see citing works
Amyloid-β pathology enhances pathological fibrillary tau seeding induced by Alzheimer PHF in vivo
Vergara, C., Houben, S., Suain, V., Yilmaz, Z., Decker, R. D., Dries, V. V., Boom, A., Mansour, S., Leroy, K., Ando, K., et al. (2018) · Acta Neuropathologica · doi:10.1007/s00401-018-1953-5 · Cited by 125 · see citing works
Uddin, M. S., Kabir, M. T., Rahman, M. S., Behl, T., Jeandet, P., Ashraf, G. M., Najda, A., Bin-Jumah, M. N., El-Seedi, H. R., & Abdel‐Daim, M. M. (2020) · International Journal of Molecular Sciences · doi:10.3390/ijms21165858 · Cited by 127 · see citing works
The role of innate immunity in Alzheimer's disease
Ennerfelt, H. E., & Lukens, J. R. (2020) · Immunological Reviews · doi:10.1111/imr.12896 · Cited by 121 · see citing works
APOE3ch alters microglial response and suppresses Aβ-induced tau seeding and spread
Chen, Y., Song, S., Parhizkar, S., Lord, J., Zhu, Y., Strickland, M. R., Wang, C., Park, J., Tabor, G. T., Jiang, H., et al. (2024) · Cell · doi:10.1016/j.cell.2023.11.029 · Cited by 120 · see citing works
Gomes, L. A., Hipp, S. A., Rijal Upadhaya, A., Balakrishnan, K., Ospitalieri, S., Koper, M. J., Largo-Barrientos, P., Uytterhoeven, V., Reichwald, J., Rabe, S., et al. (2019) · Acta Neuropathologica · doi:10.1007/s00401-019-02053-5 · Cited by 125 · see citing works
Leveraging preclinical models for the development of Alzheimer disease therapeutics
Scearce-Levie, K. A., Sanchez, P. E., & Lewcock, J. W. (2020) · Nature Reviews Drug Discovery · doi:10.1038/s41573-020-0065-9 · Cited by 118 · see citing works
Disease-Modifying Therapies for Alzheimer’s Disease: More Questions than Answers
Golde, T. E. (2022) · Neurotherapeutics · doi:10.1007/s13311-022-01201-2 · Cited by 119 · see citing works
Longitudinal 18F-MK-6240 tau tangles accumulation follows Braak stages
Pascoal, T. A., Benedet, A. L., Tudorascu, D., Therriault, J., Mathotaarachchi, S. S., Savard, M., Lussier, F. Z., Tissot, C., Chamoun, M., Kang, M. S., et al. (2021) · Brain · doi:10.1093/brain/awab248 · Cited by 113 · see citing works
Identification of altered exosomal microRNAs and mRNAs in Alzheimer's disease
Su, L., Li, R., Zhang, Z.-Q., Liu, J., Du, J., & Wei, H. (2021) · Ageing Research Reviews · doi:10.1016/j.arr.2021.101497 · Cited by 118 · see citing works
Penke, B., Szűcs, M., & Bogár, F. (2020) · Molecules · doi:10.3390/molecules25071659 · Cited by 115 · see citing works
Puntambekar, S. S., Moutinho, M., Lin, P. B.-C., Jadhav, V., Tumbleson-Brink, D., Balaji, A., Benito, M. A., Xu, G., Oblak, A., Lasagna-Reeves, C. A., et al. (2022) · Molecular Neurodegeneration · doi:10.1186/s13024-022-00545-9 · Cited by 113 · see citing works
α-Synuclein modulates tau spreading in mouse brains
Bassil, F., Meymand, E. S., Brown, H. J., Xu, H. W., Cox, T. O., Pattabhiraman, S., Maghames, C. M., Wu, Q., Zhang, B., Trojanowski, J. Q., et al. (2020) · The Journal of Experimental Medicine · doi:10.1084/jem.20192193 · Cited by 111 · see citing works
Self-citationMetformin attenuates plaque-associated tau pathology and reduces amyloid-β burden in APP/PS1 mice
Chen, Y., Zhao, S., Fan, Z., Li, Z., Zhu, Y., Shen, T., Li, K., Yan, Y., Tian, J., Liu, Z., et al. (2021) · Alzheimer's Research & Therapy · doi:10.1186/s13195-020-00761-9 · Cited by 111 · see citing works
Self-citationAyalon, G., Lee, S.-H., Adolfsson, O., Foo‐Atkins, C., Atwal, J. K., Blendstrup, M., Booler, H. S., Bravo, J., Brendza, R. P., Brunstein, F., et al. (2021) · Science Translational Medicine · doi:10.1126/scitranslmed.abb2639 · Cited by 108 · see citing works
Yang, D., Ying, J., Wang, X., Zhao, T., Yoon, S., Yang, F., Zheng, Q., Liu, X., Yu, W., & Hua, F. (2021) · Frontiers in Neuroscience · doi:10.3389/fnins.2021.654785 · Cited by 110 · see citing works
Tau reduction in the presence of amyloid-β prevents tau pathology and neuronal death in vivo
DeVos, S. L., Corjuc, B. T., Commins, C., Dujardin, S., Bannon, R. N., Corjuc, D., Moore, B. D., Bennett, R. E., Jorfi, M., Gonzales, J. A., et al. (2018) · Brain · doi:10.1093/brain/awy117 · Cited by 106 · see citing works
Alzheimer’s Disease and Diabetes: Insulin Signaling as the Bridge Linking Two Pathologies
Shieh, J. C.-C., Huang, P.-T., & Lin, Y. (2020) · Molecular Neurobiology · doi:10.1007/s12035-019-01858-5 · Cited by 104 · see citing works
Haj‐Yahya, M., Gopinath, P., Rajasekhar, K., Mirbaha, H., Diamond, M. I., & Lashuel, H. A. (2019) · Angewandte Chemie International Edition · doi:10.1002/anie.201913001 · Cited by 101 · see citing works
Li, H., Liu, C.-C., Zheng, H., & Huang, T. Y. (2018) · Translational Neurodegeneration · doi:10.1186/s40035-018-0139-3 · Cited by 103 · see citing works
Microglia and Astrocytes in Alzheimer’s Disease: Significance and Summary of Recent Advances
Deng, Q., Wu, C., Parker, E., Liu, T. C.-Y., Duan, R., & Yang, L. (2023) · Aging and disease · doi:10.14336/ad.2023.0907 · Cited by 102 · see citing works
Sun, L., Cho, H.-J., Sen, S., Arango, A. S., Huynh, T. T., Huang, Y., Bandara, N., Rogers, B. E., Tajkhorshid, E., & Mirica, L. M. (2021) · Journal of the American Chemical Society · doi:10.1021/jacs.1c05470 · Cited by 100 · see citing works
Metrick, M. A., Ferreira, N., Saijo, E., Hughson, A. G., Kraus, A., Orru, C. D., Miller, M. W., Zanusso, G., Ghetti, B. F., Vendruscolo, M., et al. (2019) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1909322116 · Cited by 99 · see citing works
Mullane, K., & Williams, M. (2018) · Biochemical Pharmacology · doi:10.1016/j.bcp.2018.09.026 · Cited by 98 · see citing works
Propagation of Tau Pathology: Integrating Insights From Postmortem and In Vivo Studies
Vogels, T., Leuzy, A., Cicognola, C., Ashton, N. J., Smolek, T., Novák, M., Blennow, K., Zetterberg, H., Hromádka, T., Žilka, N., et al. (2019) · Biological Psychiatry · doi:10.1016/j.biopsych.2019.09.019 · Cited by 94 · see citing works
Chong, J. R., Ashton, N. J., Karikari, T. K., Tanaka, T., Saridin, F. N., Reilhac, A., Robins, E. G., Nai, Y., Vrooman, H. A., Hilal, S., et al. (2021) · Alzheimer s & Dementia · doi:10.1002/alz.12332 · Cited by 93 · see citing works
- Authors
- He, Z., Guo, J. L., McBride, J. D., Narasimhan, S., Kim, H., Changolkar, L., Zhang, B., Gathagan, R. J., Yue, C., Dengler, C., Stieber, A., Nitla, M., Coulter, D. A., Abel, T., Brunden, K. R., Trojanowski, J. Q., & Lee, V. M.-Y.
- Affiliations
- University of Pennsylvania (US)
- Children's Hospital of Philadelphia (US)
- University of Iowa (US)
- Corresponding author
- Lee, Virginia M-Y
- ORCID
- Venue
- Nature Medicine
- Published
- 2017-12-04
- Volume
- 24
- Issue
- 1
- Pages
- 29-38
- ISSN
- 1078-8956 (ISSN-L)
- 1546-170X
- PMC
- PMC5760353
- OpenAlex
- W2772451653
- Cited by
- 645
- References
- 41
- Citations by year
- 2026: 44 · 2025: 67 · 2024: 100 · 2023: 71 · 2022: 91 · 2021: 99 · 2020: 87 · 2019: 49 · 2018: 36 · 2013: 1
- FWCI
- 34.82
- Type
- journal article
- Language
- en
- Open access
- green
- europepmc.org
- Licence
- Locations
- Nature Medicine (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institute on Aging (P01AG017628, P30AG010124, P01AG017586)
- Eunice Kennedy Shriver National Institute of Child Health and Human Development (U54HD086984)
- Topics
- Health Sciences › Medicine › Physiology › 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, amyloid plaques, tau pathology, tau seeding, neurofibrillary tangles, neuropil threads, dystrophic neurites, tau aggregation, transgenic mouse model
- MeSH terms
- Alzheimer Disease, Animals, Axons, Hippocampus, Humans, Amyloid beta-Peptides, Neurites, Neurofibrillary Tangles, tau Proteins, Mice
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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