The DOI matches its Crossref record; 66 of the 67 references it cites were found in a registry or an index.
Dissecting phenotypic traits linked to human resilience to Alzheimer’s pathology
Open accessAbstract
Clinico-pathological correlation studies and positron emission tomography amyloid imaging studies have shown that some individuals can tolerate substantial amounts of Alzheimer's pathology in their brains without experiencing dementia. Few details are known about the neuropathological phenotype of these unique cases that might prove relevant to understanding human resilience to Alzheimer's pathology. We conducted detailed quantitative histopathological and biochemical assessments on brains from non-demented individuals before death whose brains were free of substantial Alzheimer's pathology, non-demented individuals before death but whose post-mortem examination demonstrated significant amounts of Alzheimer's changes ('mismatches'), and demented Alzheimer's cases. Quantification of amyloid-β plaque burden, stereologically-based counts of neurofibrillary tangles, neurons and reactive glia, and morphological analyses of axons were performed in the multimodal association cortex lining the superior temporal sulcus. Levels of synaptic integrity markers, and soluble monomeric and multimeric amyloid-β and tau species were measured. Our results indicate that some individuals can accumulate equivalent loads of amyloid-β plaques and tangles to those found in demented Alzheimer's cases without experiencing dementia. Analyses revealed four main phenotypic differences among these two groups: (i) mismatches had striking preservation of neuron numbers, synaptic markers and axonal geometry compared to demented cases; (ii) demented cases had significantly higher burdens of fibrillar thioflavin-S-positive plaques and of oligomeric amyloid-β deposits reactive to conformer-specific antibody NAB61 than mismatches; (iii) strong and selective accumulation of hyperphosphorylated soluble tau multimers into the synaptic compartment was noted in demented cases compared with controls but not in mismatches; and (iv) the robust glial activation accompanying amyloid-β and tau pathologies in demented cases was remarkably reduced in mismatches. Further biochemical measurements of soluble amyloid-β species-monomers, dimers and higher molecular weight oligomers-in total brain homogenates and synaptoneurosomal preparations failed to demonstrate significant differences between mismatches and demented cases. Together, these data suggest that amyloid-β plaques and tangles do not inevitably result in neural system derangement and dementia in all individuals. We identified distinct phenotypic characteristics in the profile of brain fibrillar and soluble amyloid-β and tau accrual and in the glial response that discriminated demented and non-demented individuals with high loads of Alzheimer's pathology. Amyloid-β deposition in the form of fibrillar plaques and intimately related oligomeric amyloid-β assemblies, hyperphosphorylated soluble tau species localized in synapses, and glial activation emerged in this series as likely mediators of neurotoxicity and altered cognition, providing further insight into factors and pathways potentially involved in human susceptibility or resilience to Alzheimer's pathological changes.
Overview
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
The source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“unlike in the brains of AD subjects with dementia, no phosphorylated tau accumulation occurs within the synapses of AsymAD brains [73, 83].”
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 [73]
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“Consistent with our findings, previous studies have shown that AsymAD cases exhibit an overall deficiency in oligomeric and soluble phospho-tau species, indicating fewer pathological tau species in these cases than in AD cases [8, 73, 83].”
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 [73]
Experimental — accuracy not yet measuredThe cited source says what the claim attributes to it.
In the citing paper
“Very few studies reported using stereology to complete their cell counts,54, 70, 83, 84, 122 the gold standard for quantifying cells in a tissue without bias.”
From Markers of microglia in post-mortem brain samples from patients with Alzheimer’s disease: a systematic review (2018) · cites this paper as [83]
The cited source says what the claim attributes to it.
In the citing paper
“AsymAD brains have also been found to exhibit a neuroinflammatory profile distinct from that of AD brains, with decreased numbers of activated microglia and astrocyte cells [73]”
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 [73]
The cited source says what the claim attributes to it.
In the citing paper
“studies have demonstrated that AsymAD brains exhibit no signs of notorious synaptic or neuronal deterioration [8, 42, 73]”
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 [73]
The check wasn’t confident either way, so it gives no verdict — never disputed.
In the citing paper
“The direct connection between Aβ and MAPT pathology is poorly understood, as shown by the weak correlation between the distribution of Aβ pathology and the distribution of MAPT pathology in humans (Serrano-Pozo et al., 2011; Perez-Nievas et al., 2013; Scheltens et al., 2021).”
From β-amyloid accumulation enhances microtubule associated protein tau pathology in an APPNL-G-F/MAPTP301S mouse model of Alzheimer’s disease (2024) · cites this paper as Perez-Nievas et al., 2013
Experimental — accuracy not yet measuredIn the citing paper
“Moreover, in rare instances of AD in which cognition is relatively preserved (resilient cases), the number of neurofibrillary tangles is the same as in typical AD patients, although the amount of neuronal and synaptic loss is minimal (17).”
From All the Tau We Cannot See (2023) · cites this paper as [17]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Citations
Cites
Imaging brain amyloid in Alzheimer's disease with Pittsburgh Compound‐B
Klunk, W. E., Engler, H., Nordberg, A., Wang, Y., Blomqvist, G., Holt, D. P., Bergström, M., Savitcheva, I., Huang, G., Estrada, S., et al. (2004) · Annals of Neurology · doi:10.1002/ana.20009 · Cited by 4,496
Self-citationShankar, G. M., Li, S., Mehta, T. H., Garcia-Munoz, A., Shepardson, N. E., Smith, I., Brett, F. M., Farrell, M. A., Rowan, M. J., Lemere, C. A., et al. (2008) · Nature Medicine · doi:10.1038/nm1782 · Cited by 3,685
Harold, D., Abraham, R., Hollingworth, P., Sims, R., Gerrish, A., Hamshere, M. L., Pahwa, J. S., Moskvina, V., Dowzell, K., Williams, A., et al. (2009) · Nature Genetics · doi:10.1038/ng.440 · Cited by 3,326
The molecular pathology of Alzheimer's disease
Selkoe, D. J. (1991) · Neuron · doi:10.1016/0896-6273(91)90052-2 · Cited by 2,708
Variant of TREM2 Associated with the Risk of Alzheimer's Disease
Jonsson, T., Stefansson, H., Steinberg, S., Jonsdottir, I., Jonsson, P. V., Snaedal, J., Bjornsson, S., Huttenlocher, J., Levey, A. I., Lah, J. J., et al. (2013) · New England Journal of Medicine · doi:10.1056/nejmoa1211103 · Cited by 2,558
Synapse loss in frontal cortex biopsies in Alzheimer's disease: Correlation with cognitive severity
DeKosky, S. T., & Scheff, S. W. (1990) · Annals of Neurology · doi:10.1002/ana.410270502 · Cited by 2,376
The toxic Aβ oligomer and Alzheimer's disease: an emperor in need of clothes
Benilova, I., Karran, E., & De Strooper, B. (2012) · Nature Neuroscience · doi:10.1038/nn.3028 · Cited by 1,962
Profound Loss of Layer II Entorhinal Cortex Neurons Occurs in Very Mild Alzheimer’s Disease
Gómez-Isla, T., Price, J. L., McKeel Jr., D. W., Morris, J. C., Growdon, J. H., & Hyman, B. T. (1996) · The Journal of Neuroscience · doi:10.1523/jneurosci.16-14-04491.1996 · Cited by 1,796 · cited 5×
“Stereologically-based counts of neurofibrillary tangles, neurons, GFAP-positive astrocytes and CD68-positive microglial cells were performed as previously described (West and Gundersen, 1990; Gomez-Isla et al., 1996).”
MethodResultInfluentialSelf-citationNeuronal 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
Self-citationPropagation of Tau Pathology in a Model of Early Alzheimer's Disease
de Calignon, A., Polydoro, M., Suárez-Calvet, M., William, C., Adamowicz, D. H., Kopeikina, K. J., Pitstick, R., Sahara, N., Ashe, K. H., Carlson, G. A., et al. (2012) · Neuron · doi:10.1016/j.neuron.2011.11.033 · Cited by 1,427
Self-citation
Cited by
Sorted by citations
Religious Orders Study and Rush Memory and Aging Project
Bennett, D. A., Buchman, A. S., Boyle, P. A., Barnes, L. L., Wilson, R. S., & Schneider, J. A. (2018) · Journal of Alzheimer's Disease · doi:10.3233/jad-179939 · Cited by 1,260
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
Self-citationThe Intersection of Amyloid Beta and Tau at Synapses in Alzheimer’s Disease
Spires-Jones, T. L., & Hyman, B. T. (2014) · Neuron · doi:10.1016/j.neuron.2014.05.004 · Cited by 1,201
Self-citationRoles of tau protein in health and disease
Guo, T., Noble, W., & Hanger, D. P. (2017) · Acta Neuropathologica · doi:10.1007/s00401-017-1707-9 · Cited by 1,003
Clinical diagnosis of Alzheimer’s disease: Recommendations of the International Working Group
Dubois, B., Villain, N., Frisoni, G. B., Rabinovici, G. D., Sabbagh, M., Cappa, S., Bejanin, A., Bombois, S., Epelbaum, S., Teichmann, M., et al. (2021) · The Lancet Neurology · doi:10.1016/s1474-4422(21)00066-1 · Cited by 1,051
“…have comparable burden of AD brain lesions, confirmed with large post-mortem cohorts using quantification and digital neuropathological methods 88,89 All stages AD brain lesions (including both amyloid and tau lesions) are found in 2/3 of subjects aged of 70 years in systematic post-mortem…”
MethodA new era for understanding amyloid structures and disease
Iadanza, M. G., Jackson, M. P., Hewitt, E. W., Ranson, N. A., & Radford, S. E. (2018) · Nature Reviews Molecular Cell Biology · doi:10.1038/s41580-018-0060-8 · Cited by 1,002
López, J. A., González, H. M., & Léger, G. C. (2019) · Handbook of clinical neurology · doi:10.1016/b978-0-12-804766-8.00013-3 · Cited by 887
The Evolution of Preclinical Alzheimer’s Disease: Implications for Prevention Trials
Sperling, R., Mormino, E., & Johnson, K. (2014) · Neuron · doi:10.1016/j.neuron.2014.10.038 · Cited by 725
Eimer, W. A., Vijaya Kumar, D. K., Navalpur Shanmugam, N. K., Rodriguez, A. S., Mitchell, T., Washicosky, K. J., György, B., Breakefield, X. O., Tanzi, R. E., & Moir, R. D. (2018) · Neuron · doi:10.1016/j.neuron.2018.06.030 · Cited by 674
Interaction between Aβ and Tau in the Pathogenesis of Alzheimer’s Disease
Zhang, H., Wei, W., Zhao, M., Ma, L., Jiang, X., Pei, H., Cao, Y., & Li, H. (2021) · International Journal of Biological Sciences · doi:10.7150/ijbs.57078 · Cited by 689
At the interface of sensory and motor dysfunctions and Alzheimer’s disease.
Albers, M. W., Gilmore, G. C., Kaye, J., Murphy, C., Wingfield, A., Bennett, D. A., Boxer, A. L., Buchman, A. S., Cruickshanks, K. J., Devanand, D. P., et al. (2015) · Alzheimer's & Dementia · doi:10.1016/j.jalz.2014.04.514 · Cited by 589
Self-citationHopperton, K. E., Mohammad, D., Trépanier, M. O., Giuliano, V, & Bazinet, R. P. (2018) · Molecular Psychiatry · doi:10.1038/mp.2017.246 · Cited by 567
Type I interferon response drives neuroinflammation and synapse loss in Alzheimer disease
Roy, E. R., Wang, B., Wan, Y.-W., Chiu, G., Cole, A., Yin, Z., Propson, N. E., Xu, Y., Jankowsky, J. L., Liu, Z., et al. (2020) · Journal of Clinical Investigation · doi:10.1172/jci133737 · Cited by 563
Cascading network failure across the Alzheimer’s disease spectrum
Jones, D. T., Knopman, D. S., Gunter, J. L., Graff‐Radford, J., Vemuri, P., Boeve, B. F., Petersen, R. C., Weiner, M. W., & Jack, C. R. (2015) · Brain · doi:10.1093/brain/awv338 · Cited by 560
Self-citationSynaptic degeneration in Alzheimer disease
Tzioras, M., McGeachan, R. I., Durrant, C. S., & Spires-Jones, T. L. (2023) · Nature Reviews Neurology · doi:10.1038/s41582-022-00749-z · Cited by 504
Microglial activation and tau propagate jointly across Braak stages
Pascoal, T. A., Benedet, A. L., Ashton, N. J., Kang, M. S., Therriault, J., Chamoun, M., Savard, M., Lussier, F. Z., Tissot, C., Karikari, T. K., et al. (2021) · Nature Medicine · doi:10.1038/s41591-021-01456-w · Cited by 490
TDP-43 is a key player in the clinical features associated with Alzheimer’s disease
Josephs, K. A., Whitwell, J. L., Weigand, S. D., Murray, M. E., Tosakulwong, N., Liesinger, A. M., Petrucelli, L., Senjem, M. L., Knopman, D. S., Boeve, B. F., et al. (2014) · Acta Neuropathologica · doi:10.1007/s00401-014-1269-z · Cited by 481
Self-citationThe antimicrobial protection hypothesis of Alzheimer’s disease
Moir, R. D., Lathe, R., & Tanzi, R. E. (2018) · Alzheimer's & Dementia · doi:10.1016/j.jalz.2018.06.3040 · Cited by 456
Association of Dual-Task Gait With Incident Dementia in Mild Cognitive Impairment
Montero‐Odasso, M., Sarquis‐Adamson, Y., Speechley, M. R., BORRIE, M. J., Hachinski, V., Wells, J., Riccio, P. M., Schapira, M. C., Sejdić, E., Camicioli, R. M., et al. (2017) · JAMA Neurology · doi:10.1001/jamaneurol.2017.0643 · Cited by 401
Ferreira, S. T., Lourenco, M. V., Oliveira, M. M., & De Felice, F. G. (2015) · Frontiers in Cellular Neuroscience · doi:10.3389/fncel.2015.00191 · Cited by 373
Resistance vs resilience to Alzheimer disease
Arenaza‐Urquijo, E. M., & Vemuri, P. (2018) · Neurology · doi:10.1212/wnl.0000000000005303 · Cited by 396
The clinical promise of biomarkers of synapse damage or loss in Alzheimer’s disease
the Synaptic Health Endpoints Working Group, Colom-Cadena, M., Spires-Jones, T., Zetterberg, H., Blennow, K., Caggiano, A., DeKosky, S. T., Fillit, H., Harrison, J. E., Schneider, L. S., et al. (2020) · Alzheimer's Research & Therapy · doi:10.1186/s13195-020-00588-4 · Cited by 328
Jack, C. R., Wiste, H. J., Weigand, S. D., Rocca, W. A., Knopman, D. S., Mielke, M. M., Lowe, V. J., Senjem, M. L., Gunter, J. L., Preboske, G. M., et al. (2014) · The Lancet Neurology · doi:10.1016/s1474-4422(14)70194-2 · Cited by 358
Self-citationBeyond the neuron–cellular interactions early in Alzheimer disease pathogenesis
Henstridge, C. M., Hyman, B. T., & Spires-Jones, T. L. (2019) · Nature Reviews Neuroscience · doi:10.1038/s41583-018-0113-1 · Cited by 348
Self-citationThe identity and function of microglia in neurodegeneration
Song, W. M., & Colonna, M. (2018) · Nature Immunology · doi:10.1038/s41590-018-0212-1 · Cited by 308
Beta-amyloid deposition in chronic traumatic encephalopathy
Stein, T. D., Montenigro, P. H., Alvarez, V. E., Xia, W., Crary, J. F., Tripodis, Y., Daneshvar, D. H., Mez, J., Solomon, T., Meng, G., et al. (2015) · Acta Neuropathologica · doi:10.1007/s00401-015-1435-y · Cited by 291
Self-citationThe amyloid cascade hypothesis: an updated critical review
Kepp, K. P., Robakis, N. K. R. K., Høilund‐Carlsen, P. F., Sensi, S. L., & Vissel, B. (2023) · Brain · doi:10.1093/brain/awad159 · Cited by 315
The role of microglia in processing and spreading of bioactive tau seeds in Alzheimer’s disease
Hopp, S. C., Lin, Y., Oakley, D., Roe, A. D., DeVos, S. L., Hanlon, D., & Hyman, B. T. (2018) · Journal of Neuroinflammation · doi:10.1186/s12974-018-1309-z · Cited by 286
Self-citationSynaptic Tau Seeding Precedes Tau Pathology in Human Alzheimer’s Disease Brain
DeVos, S. L., Corjuc, B. T., Oakley, D. H., Nobuhara, C. K., Bannon, R. N., Chase, A., Commins, C., Gonzalez, J. A., Dooley, P. M., Frosch, M. P., et al. (2018) · Frontiers in Neuroscience · doi:10.3389/fnins.2018.00267 · Cited by 285
Self-citationDeciphering the astrocyte reaction in Alzheimer's disease
Perez-Nievas, B. G., & Serrano-Pozo, A. (2018) · Frontiers in Aging Neuroscience · doi:10.3389/fnagi.2018.00114 · Cited by 282
Self-citationA systems approach to stress, stressors and resilience in humans
Oken, B., Chamine, I., & Wakeland, W. W. (2014) · Behavioural Brain Research · doi:10.1016/j.bbr.2014.12.047 · Cited by 317
Alzheimer's Disease-Like Pathology Induced by Amyloid-β Oligomers in Nonhuman Primates
Forny‐Germano, L., Silva, N. M. L. E., Batista, A. F., Brito‐Moreira, J., Gralle, M., Boehnke, S. E., Coe, B. C., Lablans, A., Marques, S. A., Martinez, A. M. B., et al. (2014) · Journal of Neuroscience · doi:10.1523/jneurosci.1353-14.2014 · Cited by 245
Sekar, S., McDonald, J., Cuyugan, L., Aldrich, J., Kurdoglu, A., Adkins, J., Serrano, G., Beach, T. G., Craig, D. W., Valla, J., et al. (2015) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2014.09.027 · Cited by 199
Biomarkers for the Early Detection and Progression of Alzheimer's Disease
Counts, S. E., Ikonomovic, M. D., Mercado, N., Vega, I. E., & Mufson, E. J. (2017) · Neurotherapeutics · doi:10.1007/s13311-016-0481-z · Cited by 224
Morris, G. P., Clark, I. A., & Vissel, B. (2018) · Acta Neuropathologica · doi:10.1007/s00401-018-1918-8 · Cited by 212
Cunningham, C., & Hennessy, E. (2015) · Alzheimer's Research & Therapy · doi:10.1186/s13195-015-0117-2 · Cited by 211
Colom-Cadena, M., Davies, C., Sirisi, S., Lee, J.-E., Simzer, E. M., Tzioras, M., Querol-Vilaseca, M., Sánchez-Aced, É., Chang, Y. Y., Holt, K., et al. (2023) · Neuron · doi:10.1016/j.neuron.2023.04.020 · Cited by 224
Challenges for Alzheimer's Disease Therapy: Insights from Novel Mechanisms Beyond Memory Defects
Frozza, R. L., Lourenco, M. V., & Felice, F. G. D. (2018) · Frontiers in Neuroscience · doi:10.3389/fnins.2018.00037 · Cited by 213
The role of innate immune genes in Alzheimer's disease
Griciuc, A., & Tanzi, R. E. (2021) · Current Opinion in Neurology · doi:10.1097/wco.0000000000000911 · Cited by 192
Multiscale causal networks identify VGF as a key regulator of Alzheimer’s disease
Beckmann, N. D., Lin, W.-J., Wang, M., Cohain, A. T., Charney, A. W., Wang, P., Ma, W., Wang, Y.-C., Jiang, C., Audrain, M., et al. (2020) · Nature Communications · doi:10.1038/s41467-020-17405-z · Cited by 172
Synaptic pathology: A shared mechanism in neurological disease
Henstridge, C. M., Pickett, E. K., & Spires‐Jones, T. L. (2016) · Ageing Research Reviews · doi:10.1016/j.arr.2016.04.005 · Cited by 176
Hippocampal plasticity during the progression of Alzheimer’s disease
Mufson, E. J., Mahady, L. J., Waters, D., Counts, S., Perez, S. E., DeKosky, S. T., Ginsberg, S. D., Ikonomović, M. D., Scheff, S. W., & Binder, L. I. (2015) · Neuroscience · doi:10.1016/j.neuroscience.2015.03.006 · Cited by 184
Tau Oligomers: The Toxic Player at Synapses in Alzheimer’s Disease
Guerrero-Muñoz, M. J., Gerson, J., & Castillo-Carranza, D. L. (2015) · Frontiers in Cellular Neuroscience · doi:10.3389/fncel.2015.00464 · Cited by 168
Gómez‐Suaga, P., Perez‐Nievas, B. G., Glennon, E. B. C., Lau, D. H. W., Paillusson, S., Mórotz, G. M., Calí, T., Pizzo, P., Noble, W. J., & Miller, C. C. J. (2019) · Acta Neuropathologica Communications · doi:10.1186/s40478-019-0688-4 · Cited by 155
Self-citationNeuroinflammation, gut microbiome, and Alzheimer's disease
Lin, L., Zheng, L. J., & Zhang, L. J. (2018) · Molecular Neurobiology · doi:10.1007/s12035-018-0983-2 · Cited by 147
Is Alzheimer’s Disease Risk Modifiable?
Serrano‐Pozo, A., & Growdon, J. H. (2019) · Journal of Alzheimer s Disease · doi:10.3233/jad181028 · Cited by 169
Self-citationFlowers, S. A., & Rebeck, G. W. (2020) · Neurobiology of Disease · doi:10.1016/j.nbd.2019.104724 · Cited by 149
PSD-95 protects synapses from β-amyloid
Dore, K., Carrico, Z., Alfonso, S., Marino, M., Koymans, K., Kessels, H. W., & Malinow, R. (2021) · Cell Reports · doi:10.1016/j.celrep.2021.109194 · Cited by 149
Quaternary Structure Defines a Large Class of Amyloid-β Oligomers Neutralized by Sequestration
Liu, P., Reed, M. N., Kotilinek, L., Grant, M. K. O., Forster, C. L., Qiang, W., Shapiro, S. L., Reichl, J. H., Chiang, A. C. A., Jankowsky, J. L., et al. (2015) · Cell Reports · doi:10.1016/j.celrep.2015.05.021 · Cited by 148
Tai, H., Wang, B. Y., Serrano‐Pozo, A., Frosch, M. P., Spires‐Jones, T. L., & Hyman, B. T. (2014) · Acta Neuropathologica Communications · doi:10.1186/s40478-014-0146-2 · Cited by 147
Self-citationThe foundation and architecture of precision medicine in neurology and psychiatry
Hampel, H. J., Gao, P., Cummings, J. L., Toschi, N., Thompson, P. M., Hu, Y., Cho, M., & Vergallo, A. (2023) · Trends in Neurosciences · doi:10.1016/j.tins.2022.12.004 · Cited by 163
Markers of neuroinflammation associated with Alzheimer’s disease pathology in older adults
Popp, J., Oikonomidi, A., Tautvydaitė, D., Dayon, L., Bacher, M., Migliavacca, E., Henry, H., Kirkland, R., Severin, I., Wojcik, J., et al. (2017) · Brain, Behavior, and Immunity · doi:10.1016/j.bbi.2017.01.020 · Cited by 136
Hulle, C. V., Jonaitis, E. M., Betthauser, T. J., Batrla, R., Wild, N., Kollmorgen, G., Andréasson, U., Okonkwo, O. C., Bendlin, B. B., Asthana, S., et al. (2020) · Alzheimer s & Dementia · doi:10.1002/alz.12204 · Cited by 137
Removing endogenous tau does not prevent tau propagation yet reduces its neurotoxicity
Wegmann, S., Maury, E. A., Kirk, M. J., Saqran, L., Roe, A., DeVos, S. L., Nicholls, S., Fan, Z., Takeda, S., Cagsal‐Getkin, O., et al. (2015) · The EMBO Journal · doi:10.15252/embj.201592748 · Cited by 132
Self-citationDavis, D. H. J., Skelly, D., Murray, C., Hennessy, E., Bowen, J. S. T., Norton, S., Brayne, C., Rahkonen, T., Sulkava, R. O., Sanderson, D. J., et al. (2014) · American Journal of Geriatric Psychiatry · doi:10.1016/j.jagp.2014.08.005 · Cited by 144
Racine, A. M., Adluru, N., Alexander, A. L., Christian, B. T., Okonkwo, O. C., Oh, J., Cleary, C. A., Birdsill, A., Hillmer, A. T., Murali, D., et al. (2014) · NeuroImage: Clinical · doi:10.1016/j.nicl.2014.02.001 · Cited by 136
Distinct cytokine profiles in human brains resilient to Alzheimer's pathology
Barroeta-Espar, I., Weinstock, L. D., Perez-Nievas, B. G., Meltzer, A. C., Siao Tick Chong, M., Amaral, A. C., Murray, M. E., Moulder, K. L., Morris, J. C., Cairns, N. J., et al. (2019) · Neurobiology of Disease · doi:10.1016/j.nbd.2018.10.009 · Cited by 133
Self-citationMolecular and cellular pathophysiology of preclinical Alzheimer’s disease
Mufson, E. J., Ikonomović, M. D., Counts, S., Perez, S. E., Malek‐Ahmadi, M. H., Scheff, S. W., & Ginsberg, S. D. (2016) · Behavioural Brain Research · doi:10.1016/j.bbr.2016.05.030 · Cited by 134
Hoy, A. R., Ly, M., Carlsson, C. M., Okonkwo, O. C., Zetterberg, H., Blennow, K., Sager, M. A., Asthana, S., Johnson, S. C., Alexander, A. L., et al. (2017) · PLoS ONE · doi:10.1371/journal.pone.0173982 · Cited by 131
Moya‐Alvarado, G., Gershoni‐Emek, N., Perlson, E., & Bronfman, F. C. (2016) · Molecular & Cellular Proteomics · doi:10.1074/mcp.r115.053330 · Cited by 124
Astrocytes and neuroinflammation in Alzheimer's disease
Phillips, E. C., Croft, C. L., Crane, K., O’Neill, M. J., Hutton, M. L., Hanger, D. P., Garwood, C. J., & Noble, W. J. (2014) · Biochemical Society Transactions · doi:10.1042/bst20140155 · Cited by 115
Synaptic Amyloid-β Oligomers Precede p-Tau and Differentiate High Pathology Control Cases
Bilousova, T., Miller, C. A., Poon, W. W., Vinters, H. V., Corrada, M., Kawas, C., Hayden, E. Y., Teplow, D. B., Glabe, C., Albay, R., et al. (2016) · The American Journal of Pathology · doi:10.1016/j.ajpath.2015.09.018 · Cited by 115
Melah, K. E., Lu, S. Y.-F., Hoscheidt, S. M., Alexander, A. L., Adluru, N., Destiche, D. J., Carlsson, C. M., Zetterberg, H., Blennow, K., Okonkwo, O. C., et al. (2016) · Journal of Alzheimer s Disease · doi:10.3233/jad-150897 · Cited by 109
The metabolic brain signature of cognitive resilience in the 80+: beyond Alzheimer pathologies
Arenaza‐Urquijo, E. M., Przybelski, S. A., Lesnick, T. G., Graff‐Radford, J., Machulda, M. M., Knopman, D. S., Schwarz, C. G., Lowe, V. J., Mielke, M. M., Petersen, R. C., et al. (2019) · Brain · doi:10.1093/brain/awz037 · Cited by 115
Self-citationTau Oligomer–Containing Synapse Elimination by Microglia and Astrocytes in Alzheimer Disease
Taddei, R. N., Perbet, R., Mate de Gerando, A., Wiedmer, A. E., Sanchez-Mico, M., Connors Stewart, T., Gaona, A., Melloni, A., Amaral, A. C., Duff, K., et al. (2023) · JAMA Neurology · doi:10.1001/jamaneurol.2023.3530 · Cited by 110
Self-citationJackson, R. J., Rudinskiy, N., Herrmann, A. G., Croft, S., Kim, J. M., Petrova, V., Ramos‐Rodríguez, J. J., Pitstick, R., Wegmann, S., García-Alloza, M., et al. (2016) · European Journal of Neuroscience · doi:10.1111/ejn.13442 · Cited by 114
Self-citation[F-18]-AV-1451 binding correlates with postmortem neurofibrillary tangle Braak staging
Marquié, M., Siao Tick Chong, M., Antón-Fernández, A., Verwer, E. E., Sáez-Calveras, N., Meltzer, A. C., Ramanan, P., Amaral, A. C., Gonzalez, J., Normandin, M. D., et al. (2017) · Acta Neuropathologica · doi:10.1007/s00401-017-1740-8 · Cited by 109
Self-citationSerrano‐Pozo, A., Qian, J., Monsell, S. E., Frosch, M. P., Betensky, R. A., & Hyman, B. T. (2013) · Journal of Neuropathology & Experimental Neurology · doi:10.1097/nen.0000000000000016 · Cited by 106
Self-citationWhite, C. C., Yang, H., Yu, L., Chibnik, L. B., Dawe, R. J., Yang, J., Klein, H., Felsky, D., Ramos‐Miguel, A., Arfanakis, K., et al. (2017) · PLoS Medicine · doi:10.1371/journal.pmed.1002287 · Cited by 105
Untangling Tau and Iron: Exploring the Interaction Between Iron and Tau in Neurodegeneration
Rao, S. S., & Adlard, P. A. (2018) · Frontiers in Molecular Neuroscience · doi:10.3389/fnmol.2018.00276 · Cited by 108
The interactions of p53 with tau and Aß as potential therapeutic targets for Alzheimer’s disease
Jembrek, M. J., Slade, N., Hof, P. R., & Šimić, G. (2018) · Progress in Neurobiology · doi:10.1016/j.pneurobio.2018.05.001 · Cited by 101
Kobayashi, E., Nakano, M., Kubota, K., Himuro, N., Mizoguchi, S., Chikenji, T., Otani, M., Mizue, Y., Nagaishi, K., & Fujimiya, M. (2018) · Scientific Reports · doi:10.1038/s41598-018-19442-7 · Cited by 98
Lesions without symptoms: understanding resilience to Alzheimer disease neuropathological changes
Gómez-Isla, T., & Frosch, M. P. (2022) · Nature Reviews Neurology · doi:10.1038/s41582-022-00642-9 · Cited by 96
Self-citationReid, M. J., Beltran-Lobo, P., Johnson, L., Perez‐Nievas, B. G., & Noble, W. J. (2020) · Frontiers in Neurology · doi:10.3389/fneur.2020.572850 · Cited by 98
Self-citationDown syndrome and Alzheimer's disease: common molecular traits beyond the amyloid precursor protein
Gómez, W., Morales, R., Maracaja‐Coutinho, V., Parra, V., & Nassif, M. (2020) · Aging · doi:10.18632/aging.102677 · Cited by 94
Aβ propagation and strains: Implications for the phenotypic diversity in Alzheimer's disease
Condello, C., & Stöhr, J. (2017) · Neurobiology of Disease · doi:10.1016/j.nbd.2017.03.014 · Cited by 92
Dendritic Spines: Mediators of Cognitive Resilience in Aging and Alzheimer’s Disease
Walker, C. K., & Herskowitz, J. H. (2021) · The Neuroscientist · doi:10.1177/1073858420945964 · Cited by 86
Brody, A. H., & Strittmatter, S. M. (2017) · Advances in pharmacology · doi:10.1016/bs.apha.2017.09.007 · Cited by 89
Improving the resistance and resilience framework for aging and dementia studies
Arenaza‐Urquijo, E. M., & Vemuri, P. (2020) · Alzheimer s Research & Therapy · doi:10.1186/s13195-020-00609-2 · Cited by 84
Wood, L. B., Winslow, A. R., Proctor, E. A., McGuone, D., Mordes, D. A., Frosch, M. P., Hyman, B. T., Lauffenburger, D. A., & Haigis, K. M. (2015) · Scientific Reports · doi:10.1038/srep16622 · Cited by 83
Self-citationNanoscale structure of amyloid-β plaques in Alzheimer’s disease
Querol‐Vilaseca, M., Colom‐Cadena, M., Pegueroles, J., Núñez‐Llaves, R., Luque-Cabecerans, J., Muñoz, L., Andilla, J., Belbin, O., Spires‐Jones, T. L., Gelpí, E., et al. (2019) · Scientific Reports · doi:10.1038/s41598-019-41443-3 · Cited by 81
Zeng, X., Lafferty, T. K., Sehrawat, A., Chen, Y., Ferreira, P. C. L., Bellaver, B., Povala, G., Kamboh, M. I., Klunk, W. E., Cohen, A. D., et al. (2024) · Molecular Neurodegeneration · doi:10.1186/s13024-024-00753-5 · Cited by 91
Self-citationLin, F. V., Ren, P., Lo, R. Y., Chapman, B. P., Jacobs, A., Baran, T. M., Porsteinsson, A. P., Foxe, J. J., & Initiative, A. D. N. (2016) · Journal of Alzheimer s Disease · doi:10.3233/jad-160715 · Cited by 76
de Vries, L. E., Huitinga, I., Kessels, H. W. H. G., Swaab, D. F., & Verhaagen, J. (2024) · Molecular Neurodegeneration · doi:10.1186/s13024-024-00719-7 · Cited by 85
Autophagy in Astrocytes and its Implications in Neurodegeneration
Sung, K., & Jiménez-Sánchez, M. (2020) · Journal of Molecular Biology · doi:10.1016/j.jmb.2019.12.041 · Cited by 78
Iacono, D., Resnick, S. M., O’Brien, R., Zonderman, A. B., An, Y., Pletnikova, O., Rudow, G., Crain, B., & Troncoso, J. C. (2014) · Journal of Neuropathology & Experimental Neurology · doi:10.1097/nen.0000000000000052 · Cited by 73
PET/MR Imaging: New Frontier in Alzheimer's Disease and Other Dementias
Zhang, X. Y., Yang, Z. L., Lu, G., Yang, G. F., & Zhang, L. J. (2017) · Frontiers in Molecular Neuroscience · doi:10.3389/fnmol.2017.00343 · Cited by 75
Toden, S., Zhuang, J., Acosta, A. D., Karns, A. P., Salathia, N. S., Brewer, J. B., Wilcock, D. M., Aballi, J., Nerenberg, M. I., Quake, S. R., et al. (2020) · Science Advances · doi:10.1126/sciadv.abb1654 · Cited by 72
Belder, C. R. S., Boche, D., Nicoll, J. A. R., Jaunmuktane, Z., Zetterberg, H., Schott, J. M., Barkhof, F., & Fox, N. C. (2024) · The Lancet Neurology · doi:10.1016/s1474-4422(24)00335-1 · Cited by 79
Cuervo-Zanatta, D., Syeda, T., Sánchez-Valle, V., Irene-Fierro, M., Torres‐Aguilar, P. C., Torres-Ramos, M., Shibayama-Salas, M., Silva-Olivares, A., Noriega, L. G., Torres, N., et al. (2022) · Cellular and Molecular Neurobiology · doi:10.1007/s10571-022-01268-7 · Cited by 76
Ribarič, S. (2022) · International Journal of Molecular Sciences · doi:10.3390/ijms23063245 · Cited by 77
Physiological and Pathophysiological Implications of Synaptic Tau
Regan, P. L., Whitcomb, D. J., & Cho, K. (2016) · The Neuroscientist · doi:10.1177/1073858416633439 · Cited by 75
The Role of P2X7 Receptor in Alzheimer’s Disease
Francistiová, L., Bianchi, C., Lauro, C. D., Sebastián‐Serrano, Á., de Diego-García, L., Kobolák, J., Dinnyés, A., & Díaz-Hernández, M. (2020) · Frontiers in Molecular Neuroscience · doi:10.3389/fnmol.2020.00094 · Cited by 73
Furcila, D., DeFelipe, J., & Alonso‐Nanclares, L. (2018) · Journal of Alzheimer s Disease · doi:10.3233/jad-180173 · Cited by 73
Role of SNAREs in Neurodegenerative Diseases
Margiotta, A. (2021) · Cells · doi:10.3390/cells10050991 · Cited by 70
Translational approaches to understanding resilience to Alzheimer’s disease
Neuner, S. M., Telpoukhovskaia, M., Menon, V., O’Connell, K. M. S., Hohman, T. J., & Kaczorowski, C. C. (2022) · Trends in Neurosciences · doi:10.1016/j.tins.2022.02.005 · Cited by 68
“Interestingly, studies have found that resilient individuals have lower levels of hyperphosphorylated tau accumulation in the synaptic compartment [7] and neocortical areas [11], despite comparable levels of amyloid.”
BackgroundResultInfluentialMicroglia: Friend and foe in tauopathy
Odfalk, K. F., Bieniek, K. F., & Hopp, S. C. (2022) · Progress in Neurobiology · doi:10.1016/j.pneurobio.2022.102306 · Cited by 60
Wang, S., Li, B., Solomon, V. A., Fonteh, A. N., Rapoport, S. I., Bennett, D. A., Arvanitakis, Z., Chui, H. C., Sullivan, P. M., & Yassine, H. N. (2022) · Molecular Neurodegeneration · doi:10.1186/s13024-022-00549-5 · Cited by 68
β-Amyloid Induces Pathology-Related Patterns of Tau Hyperphosphorylation at Synaptic Terminals
Wu, H., Kuo, P.-C., Wang, Y.-T., Lin, H.-T., Roe, A. D., Wang, B. Y., Han, C., Hyman, B. T., Chen, Y., & Tai, H. (2018) · Journal of Neuropathology & Experimental Neurology · doi:10.1093/jnen/nly059 · Cited by 72
Self-citationLithium as a Treatment for Alzheimer’s Disease: The Systems Pharmacology Perspective
Hampel, H. J., Lista, S., Mango, D., Nisticò, R., Perry, G. L., Ávila, J., Hernández, F., Geerts, H., Vergallo, A., (APMI), A. P. M. I., et al. (2019) · Journal of Alzheimer s Disease · doi:10.3233/jad-190197 · Cited by 67
Metadata
- Authors
- Perez-Nievas, B. G., Stein, T. D., Tai, H.-C., Dols-Icardo, O., Scotton, T. C., Barroeta-Espar, I., Fernandez-Carballo, L., de Munain, E. L., Perez, J., Marquie, M., Serrano-Pozo, A., Frosch, M. P., Lowe, V., Parisi, J. E., Petersen, R. C., Ikonomovic, M. D., López, O. L., Klunk, W., Hyman, B. T., & Gómez-Isla, T.
- Affiliations
- Harvard University (US)
- Mayo Clinic (US)
- University of Pittsburgh (US)
- ORCID
- Venue
- Brain
- Publisher
- Oxford University Press (OUP)
- Published
- 2013-07-03
- Volume
- 136
- Issue
- 8
- Pages
- 2510-2526
- ISSN
- 0006-8950 (ISSN-L)
- 1460-2156
- PMC
- PMC3722351
- OpenAlex
- W1978991736
- Cited by
- 387
- References
- 67
- Citations by year
- 2026: 30 · 2025: 27 · 2024: 28 · 2023: 38 · 2022: 34 · 2021: 46 · 2020: 37 · 2019: 29 · 2018: 36 · 2017: 18 · 2016: 18 · 2015: 22 · 2014: 20 · 2013: 3
- FWCI
- 14.58
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Brain (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Research Portal (King's College London) (submittedVersion)
- Funders
- U.S. Department of Veterans Affairs (I01 CX001038)
- National Institutes of Health
- National Institute on Aging (AG-005133, R01AG043511, P50AG005133, U01AG016976, P50AG005134, P30AG062421, P50AG016574)
- 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, amyloid plaques, neurofibrillary tangles, tau hyperphosphorylation, soluble amyloid-beta oligomers, synaptic integrity, axon morphology, glial activation, superior temporal sulcus, association cortex, dementia
- MeSH terms
- Aged, Aged, 80 and over, Alzheimer Disease, Brain, Cognition, Humans, Neuroglia, Neurons, Phenotype, Neurofibrillary Tangles, tau Proteins, Resilience, Psychological, Plaque, Amyloid
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 ›
Are you an author, or do you see a problem with this page? Request a review
