Cited by 443Neuroinflammation and Neurodegeneration MechanismsAlzheimer's disease research and treatmentsDementia and Cognitive Impairment Research

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Distinct amyloid-β and tau-associated microglia profiles in Alzheimer’s disease

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Gerrits, Emma, Brouwer, Nieske, Kooistra, Susanne M., Woodbury, Maya E., Vermeiren, Yannick, Lambourne, Mirjam, Mulder, Jan, Kummer, Markus, Möller, Thomas, Biber, Knut, Dunnen, Wilfred F. A. den, De Deyn, Peter P., Eggen, Bart J. L., Boddeke, Erik W. G. M.·2021·Acta Neuropathologica

DOI 10.1007/s00401-021-02263-wPMC PMC8043951

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Abstract

Alzheimer’s disease (AD) is the most prevalent form of dementia and is characterized by abnormal extracellular aggregates of amyloid-β and intraneuronal hyperphosphorylated tau tangles and neuropil threads. Microglia, the tissue-resident macrophages of the central nervous system (CNS), are important for CNS homeostasis and implicated in AD pathology. In amyloid mouse models, a phagocytic/activated microglia phenotype has been identified. How increasing levels of amyloid-β and tau pathology affect human microglia transcriptional profiles is unknown. Here, we performed snRNAseq on 482,472 nuclei from non-demented control brains and AD brains containing only amyloid-β plaques or both amyloid-β plaques and tau pathology. Within the microglia population, distinct expression profiles were identified of which two were AD pathology-associated. The phagocytic/activated AD1-microglia population abundance strongly correlated with tissue amyloid-β load and localized to amyloid-β plaques. The AD2-microglia abundance strongly correlated with tissue phospho-tau load and these microglia were more abundant in samples with overt tau pathology. This full characterization of human disease-associated microglia phenotypes provides new insights in the pathophysiological role of microglia in AD and offers new targets for microglia-state-specific therapeutic strategies.

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Additional file 6 of Molecular and spatial heterogeneity of microglia in Rasmussen encephalitis
Westfall, J. J., Schwind, W. N., Sran, S., Navarro, J. B., Leonard, J., Pindrik, J. A., Pierson, C. R., Boué, D. R., Koboldt, D. C., Ostendorf, A. P., et al. (2022) · Figshare · doi:10.6084/m9.figshare.21601437
Additional file 3 of Microglia phenotypes are associated with subregional patterns of concomitant tau, amyloid-β and α-synuclein pathologies in the hippocampus of patients with Alzheimer’s disease and dementia with Lewy bodies
Fixemer, S., Ameli, C., Hammer, G. P., Salamanca, L., Huarte, O. U., Schwartz, C., Gérardy, J.-J., Mechawar, N., Skupin, A., Mittelbronn, M., et al. (2022) · Figshare · doi:10.6084/m9.figshare.19373331
Additional file 2 of Brain macrophages acquire distinct transcriptomes in multiple sclerosis lesions and normal appearing white matter
Miedema, A., Gerrits, E., Brouwer, N., Jiang, Q., Kracht, L., Meijer, M., Nutma, E., Peferoen-Baert, R. M. B., Pijnacker, A. T. E., Wesseling, E. M., et al. (2022) · Figshare · doi:10.6084/m9.figshare.19090710
Self-citation
Additional file 5 of Amyloid-beta and tau pathologies act synergistically to induce novel disease stage-specific microglia subtypes
Kim, D. W., Tu, K. J., Wei, A., Lau, A., Gonzalez-Gil, A., Cao, T., Braunstein, K. E., Ling, J. P., Troncoso, J. C., Wong, P. C., et al. (2024) · Figshare · doi:10.6084/m9.figshare.26555684
Additional file 4 of Brain macrophages acquire distinct transcriptomes in multiple sclerosis lesions and normal appearing white matter
Miedema, A., Gerrits, E., Brouwer, N., Jiang, Q., Kracht, L., Meijer, M., Nutma, E., Peferoen-Baert, R. M. B., Pijnacker, A. T. E., Wesseling, E. M., et al. (2022) · Figshare · doi:10.6084/m9.figshare.19090716
Self-citation
Additional file 8 of Herpes simplex virus 1 accelerates the progression of Alzheimer’s disease by modulating microglial phagocytosis and activating NLRP3 pathway
Wang, Z., Liu, J., Han, J., Zhang, T., Li, S., Hou, Y., Su, H., Han, F., & Zhang, C. (2024) · Figshare · doi:10.6084/m9.figshare.26751314
Additional file 17 of Amyloid-beta and tau pathologies act synergistically to induce novel disease stage-specific microglia subtypes
Kim, D. W., Tu, K. J., Wei, A., Lau, A., Gonzalez-Gil, A., Cao, T., Braunstein, K. E., Ling, J. P., Troncoso, J. C., Wong, P. C., et al. (2024) · Figshare · doi:10.6084/m9.figshare.26555720
Additional file 6 of Single-cell RNA sequencing reveals the evolution of the immune landscape during perihematomal edema progression after intracerebral hemorrhage
Zhang, P., Gao, C., Guo, Q., Yang, D., Zhang, G., Lu, H., Zhang, L., Zhang, G., & Li, D. (2024) · Figshare · doi:10.6084/m9.figshare.26726468
Additional file 5 of Rise and fall of peroxisomes during Alzheimer´s disease: a pilot study in human brains
Semikasev, E., Ahlemeyer, B., Acker, T., Schänzer, A., & Baumgart‐Vogt, E. (2024) · Figshare · doi:10.6084/m9.figshare.26588847
Additional file 9 of Amyloid-beta and tau pathologies act synergistically to induce novel disease stage-specific microglia subtypes
Kim, D. W., Tu, K. J., Wei, A., Lau, A., Gonzalez-Gil, A., Cao, T., Braunstein, K. E., Ling, J. P., Troncoso, J. C., Wong, P. C., et al. (2024) · Figshare · doi:10.6084/m9.figshare.26555696
Additional file 4 of Molecular and spatial heterogeneity of microglia in Rasmussen encephalitis
Westfall, J. J., Schwind, W. N., Sran, S., Navarro, J. B., Leonard, J., Pindrik, J. A., Pierson, C. R., Boué, D. R., Koboldt, D. C., Ostendorf, A. P., et al. (2022) · Figshare · doi:10.6084/m9.figshare.21601431
Additional file 3 of Herpes simplex virus 1 accelerates the progression of Alzheimer’s disease by modulating microglial phagocytosis and activating NLRP3 pathway
Wang, Z., Liu, J., Han, J., Zhang, T., Li, S., Hou, Y., Su, H., Han, F., & Zhang, C. (2024) · Figshare · doi:10.6084/m9.figshare.26751299
Additional file 6 of Rise and fall of peroxisomes during Alzheimer´s disease: a pilot study in human brains
Semikasev, E., Ahlemeyer, B., Acker, T., Schänzer, A., & Baumgart‐Vogt, E. (2024) · Figshare · doi:10.6084/m9.figshare.26588850
Additional file 1 of Microglial activation, tau and amyloid deposition in TREM2 p.R47H carriers and mild cognitive impairment patients: a multi-modal/multi-tracer PET/MRI imaging study with influenza vaccine immune challenge
Cousins, O., Schubert, J. J., Chandra, A., Veronese, M., Valkimadi, P., Creese, B., Khan, Z., Arathimos, R., Hampshire, A., Rosenzweig, I., et al. (2023) · Figshare · doi:10.6084/m9.figshare.24603603
Additional file 3 of Single-cell RNA sequencing reveals the evolution of the immune landscape during perihematomal edema progression after intracerebral hemorrhage
Zhang, P., Gao, C., Guo, Q., Yang, D., Zhang, G., Lu, H., Zhang, L., Zhang, G., & Li, D. (2024) · Figshare · doi:10.6084/m9.figshare.26726459
Additional file 8 of Amyloid-beta and tau pathologies act synergistically to induce novel disease stage-specific microglia subtypes
Kim, D. W., Tu, K. J., Wei, A., Lau, A., Gonzalez-Gil, A., Cao, T., Braunstein, K. E., Ling, J. P., Troncoso, J. C., Wong, P. C., et al. (2024) · Figshare · doi:10.6084/m9.figshare.26555693
Additional file 2 of Herpes simplex virus 1 accelerates the progression of Alzheimer’s disease by modulating microglial phagocytosis and activating NLRP3 pathway
Wang, Z., Liu, J., Han, J., Zhang, T., Li, S., Hou, Y., Su, H., Han, F., & Zhang, C. (2024) · Figshare · doi:10.6084/m9.figshare.26751296
Additional file 11 of Single-cell RNA sequencing reveals the evolution of the immune landscape during perihematomal edema progression after intracerebral hemorrhage
Zhang, P., Gao, C., Guo, Q., Yang, D., Zhang, G., Lu, H., Zhang, L., Zhang, G., & Li, D. (2024) · Figshare · doi:10.6084/m9.figshare.26726483
Additional file 7 of Molecular and spatial heterogeneity of microglia in Rasmussen encephalitis
Westfall, J. J., Schwind, W. N., Sran, S., Navarro, J. B., Leonard, J., Pindrik, J. A., Pierson, C. R., Boué, D. R., Koboldt, D. C., Ostendorf, A. P., et al. (2022) · Figshare · doi:10.6084/m9.figshare.21601440
Additional file 10 of Single-cell RNA sequencing reveals the evolution of the immune landscape during perihematomal edema progression after intracerebral hemorrhage
Zhang, P., Gao, C., Guo, Q., Yang, D., Zhang, G., Lu, H., Zhang, L., Zhang, G., & Li, D. (2024) · Figshare · doi:10.6084/m9.figshare.26726480
Additional file 8 of Molecular and spatial heterogeneity of microglia in Rasmussen encephalitis
Westfall, J. J., Schwind, W. N., Sran, S., Navarro, J. B., Leonard, J., Pindrik, J. A., Pierson, C. R., Boué, D. R., Koboldt, D. C., Ostendorf, A. P., et al. (2022) · Figshare · doi:10.6084/m9.figshare.21601443
Additional file 3 of Molecular and spatial heterogeneity of microglia in Rasmussen encephalitis
Westfall, J. J., Schwind, W. N., Sran, S., Navarro, J. B., Leonard, J., Pindrik, J. A., Pierson, C. R., Boué, D. R., Koboldt, D. C., Ostendorf, A. P., et al. (2022) · Figshare · doi:10.6084/m9.figshare.21601428
Additional file 2 of Molecular and spatial heterogeneity of microglia in Rasmussen encephalitis
Westfall, J. J., Schwind, W. N., Sran, S., Navarro, J. B., Leonard, J., Pindrik, J. A., Pierson, C. R., Boué, D. R., Koboldt, D. C., Ostendorf, A. P., et al. (2022) · Figshare · doi:10.6084/m9.figshare.21601425
Additional file 8 of Single-cell RNA sequencing reveals the evolution of the immune landscape during perihematomal edema progression after intracerebral hemorrhage
Zhang, P., Gao, C., Guo, Q., Yang, D., Zhang, G., Lu, H., Zhang, L., Zhang, G., & Li, D. (2024) · Figshare · doi:10.6084/m9.figshare.26726474
Additional file 15 of Amyloid-beta and tau pathologies act synergistically to induce novel disease stage-specific microglia subtypes
Kim, D. W., Tu, K. J., Wei, A., Lau, A., Gonzalez-Gil, A., Cao, T., Braunstein, K. E., Ling, J. P., Troncoso, J. C., Wong, P. C., et al. (2024) · Figshare · doi:10.6084/m9.figshare.26555714
Additional file 3 of Rise and fall of peroxisomes during Alzheimer´s disease: a pilot study in human brains
Semikasev, E., Ahlemeyer, B., Acker, T., Schänzer, A., & Baumgart‐Vogt, E. (2024) · Figshare · doi:10.6084/m9.figshare.26588841
Additional file 7 of Microglia phenotypes are associated with subregional patterns of concomitant tau, amyloid-β and α-synuclein pathologies in the hippocampus of patients with Alzheimer’s disease and dementia with Lewy bodies
Fixemer, S., Ameli, C., Hammer, G. P., Salamanca, L., Huarte, O. U., Schwartz, C., Gérardy, J.-J., Mechawar, N., Skupin, A., Mittelbronn, M., et al. (2022) · Figshare · doi:10.6084/m9.figshare.19373346
Additional file 16 of Amyloid-beta and tau pathologies act synergistically to induce novel disease stage-specific microglia subtypes
Kim, D. W., Tu, K. J., Wei, A., Lau, A., Gonzalez-Gil, A., Cao, T., Braunstein, K. E., Ling, J. P., Troncoso, J. C., Wong, P. C., et al. (2024) · Figshare · doi:10.6084/m9.figshare.26555717
Additional file 4 of Brain matters: unveiling the distinct contributions of region, age, and sex to glia diversity and CNS function
Seeker, L. A., Bestard-Cuche, N., Jäkel, S., Kazakou, N.-L., Bøstrand, S. M. K., Wagstaff, L. J., Cholewa-Waclaw, J., Kilpatrick, A. M., van Bruggen, D., Kabbe, M., et al. (2024) · Figshare · doi:10.6084/m9.figshare.26591057
Additional file 2 of Brain matters: unveiling the distinct contributions of region, age, and sex to glia diversity and CNS function
Seeker, L. A., Bestard-Cuche, N., Jäkel, S., Kazakou, N.-L., Bøstrand, S. M. K., Wagstaff, L. J., Cholewa-Waclaw, J., Kilpatrick, A. M., van Bruggen, D., Kabbe, M., et al. (2024) · Figshare · doi:10.6084/m9.figshare.26591051
Additional file 5 of Herpes simplex virus 1 accelerates the progression of Alzheimer’s disease by modulating microglial phagocytosis and activating NLRP3 pathway
Wang, Z., Liu, J., Han, J., Zhang, T., Li, S., Hou, Y., Su, H., Han, F., & Zhang, C. (2024) · Figshare · doi:10.6084/m9.figshare.26751305
Additional file 6 of Amyloid-beta and tau pathologies act synergistically to induce novel disease stage-specific microglia subtypes
Kim, D. W., Tu, K. J., Wei, A., Lau, A., Gonzalez-Gil, A., Cao, T., Braunstein, K. E., Ling, J. P., Troncoso, J. C., Wong, P. C., et al. (2024) · Figshare · doi:10.6084/m9.figshare.26555687
Additional file 9 of Herpes simplex virus 1 accelerates the progression of Alzheimer’s disease by modulating microglial phagocytosis and activating NLRP3 pathway
Wang, Z., Liu, J., Han, J., Zhang, T., Li, S., Hou, Y., Su, H., Han, F., & Zhang, C. (2024) · Figshare · doi:10.6084/m9.figshare.26751317
Additional file 1 of Brain matters: unveiling the distinct contributions of region, age, and sex to glia diversity and CNS function
Seeker, L. A., Bestard-Cuche, N., Jäkel, S., Kazakou, N.-L., Bøstrand, S. M. K., Wagstaff, L. J., Cholewa-Waclaw, J., Kilpatrick, A. M., van Bruggen, D., Kabbe, M., et al. (2024) · Figshare · doi:10.6084/m9.figshare.26591048
Additional file 13 of Single-cell RNA sequencing reveals the evolution of the immune landscape during perihematomal edema progression after intracerebral hemorrhage
Zhang, P., Gao, C., Guo, Q., Yang, D., Zhang, G., Lu, H., Zhang, L., Zhang, G., & Li, D. (2024) · Figshare · doi:10.6084/m9.figshare.26726489
Additional file 7 of Amyloid-beta and tau pathologies act synergistically to induce novel disease stage-specific microglia subtypes
Kim, D. W., Tu, K. J., Wei, A., Lau, A., Gonzalez-Gil, A., Cao, T., Braunstein, K. E., Ling, J. P., Troncoso, J. C., Wong, P. C., et al. (2024) · Figshare · doi:10.6084/m9.figshare.26555690
Additional file 4 of Herpes simplex virus 1 accelerates the progression of Alzheimer’s disease by modulating microglial phagocytosis and activating NLRP3 pathway
Wang, Z., Liu, J., Han, J., Zhang, T., Li, S., Hou, Y., Su, H., Han, F., & Zhang, C. (2024) · Figshare · doi:10.6084/m9.figshare.26751302
Additional file 9 of Single-cell RNA sequencing reveals the evolution of the immune landscape during perihematomal edema progression after intracerebral hemorrhage
Zhang, P., Gao, C., Guo, Q., Yang, D., Zhang, G., Lu, H., Zhang, L., Zhang, G., & Li, D. (2024) · Figshare · doi:10.6084/m9.figshare.26726477
Additional file 11 of Amyloid-beta and tau pathologies act synergistically to induce novel disease stage-specific microglia subtypes
Kim, D. W., Tu, K. J., Wei, A., Lau, A., Gonzalez-Gil, A., Cao, T., Braunstein, K. E., Ling, J. P., Troncoso, J. C., Wong, P. C., et al. (2024) · Figshare · doi:10.6084/m9.figshare.26555702
Additional file 1 of Monocyte-derived cells invade brain parenchyma and amyloid plaques in human Alzheimer’s disease hippocampus
Muñoz‐Castro, C., Mejias‐Ortega, M., Sánchez‐Mejías, E., Navarro, V., Trujillo‐Estrada, L., Jiménez, S., León, J. A. G., Fernandez-Valenzuela, J. J., Sanchez-Mico, M. V., Romero‐Molina, C., et al. (2024) · Figshare · doi:10.6084/m9.figshare.26571967
Additional file 10 of Molecular and spatial heterogeneity of microglia in Rasmussen encephalitis
Westfall, J. J., Schwind, W. N., Sran, S., Navarro, J. B., Leonard, J., Pindrik, J. A., Pierson, C. R., Boué, D. R., Koboldt, D. C., Ostendorf, A. P., et al. (2022) · Figshare · doi:10.6084/m9.figshare.21601404
Additional file 2 of Microglia phenotypes are associated with subregional patterns of concomitant tau, amyloid-β and α-synuclein pathologies in the hippocampus of patients with Alzheimer’s disease and dementia with Lewy bodies
Fixemer, S., Ameli, C., Hammer, G. P., Salamanca, L., Huarte, O. U., Schwartz, C., Gérardy, J.-J., Mechawar, N., Skupin, A., Mittelbronn, M., et al. (2022) · Figshare · doi:10.6084/m9.figshare.19373328
Additional file 1 of Herpes simplex virus 1 accelerates the progression of Alzheimer’s disease by modulating microglial phagocytosis and activating NLRP3 pathway
Wang, Z., Liu, J., Han, J., Zhang, T., Li, S., Hou, Y., Su, H., Han, F., & Zhang, C. (2024) · Figshare · doi:10.6084/m9.figshare.26751293
Additional file 1 of Single-cell RNA sequencing reveals the evolution of the immune landscape during perihematomal edema progression after intracerebral hemorrhage
Zhang, P., Gao, C., Guo, Q., Yang, D., Zhang, G., Lu, H., Zhang, L., Zhang, G., & Li, D. (2024) · Figshare · doi:10.6084/m9.figshare.25918980
Additional file 4 of Amyloid-beta and tau pathologies act synergistically to induce novel disease stage-specific microglia subtypes
Kim, D. W., Tu, K. J., Wei, A., Lau, A., Gonzalez-Gil, A., Cao, T., Braunstein, K. E., Ling, J. P., Troncoso, J. C., Wong, P. C., et al. (2024) · Figshare · doi:10.6084/m9.figshare.26555681
Additional file 6 of Brain matters: unveiling the distinct contributions of region, age, and sex to glia diversity and CNS function
Seeker, L. A., Bestard-Cuche, N., Jäkel, S., Kazakou, N.-L., Bøstrand, S. M. K., Wagstaff, L. J., Cholewa-Waclaw, J., Kilpatrick, A. M., van Bruggen, D., Kabbe, M., et al. (2024) · Figshare · doi:10.6084/m9.figshare.26591063
Additional file 5 of Single-cell RNA sequencing reveals the evolution of the immune landscape during perihematomal edema progression after intracerebral hemorrhage
Zhang, P., Gao, C., Guo, Q., Yang, D., Zhang, G., Lu, H., Zhang, L., Zhang, G., & Li, D. (2024) · Figshare · doi:10.6084/m9.figshare.26726465
Additional file 1 of Amyloid-beta and tau pathologies act synergistically to induce novel disease stage-specific microglia subtypes
Kim, D. W., Tu, K. J., Wei, A., Lau, A., Gonzalez-Gil, A., Cao, T., Braunstein, K. E., Ling, J. P., Troncoso, J. C., Wong, P. C., et al. (2024) · Figshare · doi:10.6084/m9.figshare.26555672
Additional file 8 of Microglia phenotypes are associated with subregional patterns of concomitant tau, amyloid-β and α-synuclein pathologies in the hippocampus of patients with Alzheimer’s disease and dementia with Lewy bodies
Fixemer, S., Ameli, C., Hammer, G. P., Salamanca, L., Huarte, O. U., Schwartz, C., Gérardy, J.-J., Mechawar, N., Skupin, A., Mittelbronn, M., et al. (2022) · Figshare · doi:10.6084/m9.figshare.19373352
Additional file 9 of Molecular and spatial heterogeneity of microglia in Rasmussen encephalitis
Westfall, J. J., Schwind, W. N., Sran, S., Navarro, J. B., Leonard, J., Pindrik, J. A., Pierson, C. R., Boué, D. R., Koboldt, D. C., Ostendorf, A. P., et al. (2022) · Figshare · doi:10.6084/m9.figshare.21601446
Additional file 13 of Amyloid-beta and tau pathologies act synergistically to induce novel disease stage-specific microglia subtypes
Kim, D. W., Tu, K. J., Wei, A., Lau, A., Gonzalez-Gil, A., Cao, T., Braunstein, K. E., Ling, J. P., Troncoso, J. C., Wong, P. C., et al. (2024) · Figshare · doi:10.6084/m9.figshare.26555708
Additional file 2 of Amyloid-beta and tau pathologies act synergistically to induce novel disease stage-specific microglia subtypes
Kim, D. W., Tu, K. J., Wei, A., Lau, A., Gonzalez-Gil, A., Cao, T., Braunstein, K. E., Ling, J. P., Troncoso, J. C., Wong, P. C., et al. (2024) · Figshare · doi:10.6084/m9.figshare.26555675
Additional file 3 of Amyloid-beta and tau pathologies act synergistically to induce novel disease stage-specific microglia subtypes
Kim, D. W., Tu, K. J., Wei, A., Lau, A., Gonzalez-Gil, A., Cao, T., Braunstein, K. E., Ling, J. P., Troncoso, J. C., Wong, P. C., et al. (2024) · Figshare · doi:10.6084/m9.figshare.26555678
Additional file 6 of Microglia phenotypes are associated with subregional patterns of concomitant tau, amyloid-β and α-synuclein pathologies in the hippocampus of patients with Alzheimer’s disease and dementia with Lewy bodies
Fixemer, S., Ameli, C., Hammer, G. P., Salamanca, L., Huarte, O. U., Schwartz, C., Gérardy, J.-J., Mechawar, N., Skupin, A., Mittelbronn, M., et al. (2022) · Figshare · doi:10.6084/m9.figshare.19373343
Additional file 5 of Brain macrophages acquire distinct transcriptomes in multiple sclerosis lesions and normal appearing white matter
Miedema, A., Gerrits, E., Brouwer, N., Jiang, Q., Kracht, L., Meijer, M., Nutma, E., Peferoen-Baert, R. M. B., Pijnacker, A. T. E., Wesseling, E. M., et al. (2022) · Figshare · doi:10.6084/m9.figshare.19090719
Self-citation
Additional file 4 of Microglia phenotypes are associated with subregional patterns of concomitant tau, amyloid-β and α-synuclein pathologies in the hippocampus of patients with Alzheimer’s disease and dementia with Lewy bodies
Fixemer, S., Ameli, C., Hammer, G. P., Salamanca, L., Huarte, O. U., Schwartz, C., Gérardy, J.-J., Mechawar, N., Skupin, A., Mittelbronn, M., et al. (2022) · Figshare · doi:10.6084/m9.figshare.19373334
Additional file 3 of Brain macrophages acquire distinct transcriptomes in multiple sclerosis lesions and normal appearing white matter
Miedema, A., Gerrits, E., Brouwer, N., Jiang, Q., Kracht, L., Meijer, M., Nutma, E., Peferoen-Baert, R. M. B., Pijnacker, A. T. E., Wesseling, E. M., et al. (2022) · Figshare · doi:10.6084/m9.figshare.19090713
Self-citation
Additional file 1 of Molecular and spatial heterogeneity of microglia in Rasmussen encephalitis
Westfall, J. J., Schwind, W. N., Sran, S., Navarro, J. B., Leonard, J., Pindrik, J. A., Pierson, C. R., Boué, D. R., Koboldt, D. C., Ostendorf, A. P., et al. (2022) · Figshare · doi:10.6084/m9.figshare.21601422
Additional file 1 of Brain macrophages acquire distinct transcriptomes in multiple sclerosis lesions and normal appearing white matter
Miedema, A., Gerrits, E., Brouwer, N., Jiang, Q., Kracht, L., Meijer, M., Nutma, E., Peferoen-Baert, R. M. B., Pijnacker, A. T. E., Wesseling, E. M., et al. (2022) · Figshare · doi:10.6084/m9.figshare.19090707
Self-citation
Additional file 1 of Regulating microglial miR-155 transcriptional phenotype alleviates Alzheimer’s-induced retinal vasculopathy by limiting Clec7a/Galectin-3+ neurodegenerative microglia
Shi, H., Yin, Z., Koronyo, Y., Fuchs, D.-T., Sheyn, J., Davis, M. R., Wilson, J. W., Margeta, M. A., Pitts, K. M., Herron, S., et al. (2022) · Figshare · doi:10.6084/m9.figshare.21069636
Additional file 1 of Rise and fall of peroxisomes during Alzheimer´s disease: a pilot study in human brains
Semikasev, E., Ahlemeyer, B., Acker, T., Schänzer, A., & Baumgart‐Vogt, E. (2024) · Figshare · doi:10.6084/m9.figshare.26588829
Additional file 2 of Single-cell RNA sequencing reveals the evolution of the immune landscape during perihematomal edema progression after intracerebral hemorrhage
Zhang, P., Gao, C., Guo, Q., Yang, D., Zhang, G., Lu, H., Zhang, L., Zhang, G., & Li, D. (2024) · Figshare · doi:10.6084/m9.figshare.25919061
Additional file 10 of Amyloid-beta and tau pathologies act synergistically to induce novel disease stage-specific microglia subtypes
Kim, D. W., Tu, K. J., Wei, A., Lau, A., Gonzalez-Gil, A., Cao, T., Braunstein, K. E., Ling, J. P., Troncoso, J. C., Wong, P. C., et al. (2024) · Figshare · doi:10.6084/m9.figshare.26555699
Additional file 12 of Single-cell RNA sequencing reveals the evolution of the immune landscape during perihematomal edema progression after intracerebral hemorrhage
Zhang, P., Gao, C., Guo, Q., Yang, D., Zhang, G., Lu, H., Zhang, L., Zhang, G., & Li, D. (2024) · Figshare · doi:10.6084/m9.figshare.26726486
Additional file 7 of Rise and fall of peroxisomes during Alzheimer´s disease: a pilot study in human brains
Semikasev, E., Ahlemeyer, B., Acker, T., Schänzer, A., & Baumgart‐Vogt, E. (2024) · Figshare · doi:10.6084/m9.figshare.26588853
Additional file 4 of Rise and fall of peroxisomes during Alzheimer´s disease: a pilot study in human brains
Semikasev, E., Ahlemeyer, B., Acker, T., Schänzer, A., & Baumgart‐Vogt, E. (2024) · Figshare · doi:10.6084/m9.figshare.26588844
Additional file 10 of Herpes simplex virus 1 accelerates the progression of Alzheimer’s disease by modulating microglial phagocytosis and activating NLRP3 pathway
Wang, Z., Liu, J., Han, J., Zhang, T., Li, S., Hou, Y., Su, H., Han, F., & Zhang, C. (2024) · Figshare · doi:10.6084/m9.figshare.26751320
Additional file 7 of Herpes simplex virus 1 accelerates the progression of Alzheimer’s disease by modulating microglial phagocytosis and activating NLRP3 pathway
Wang, Z., Liu, J., Han, J., Zhang, T., Li, S., Hou, Y., Su, H., Han, F., & Zhang, C. (2024) · Figshare · doi:10.6084/m9.figshare.26751311
Additional file 11 of Molecular and spatial heterogeneity of microglia in Rasmussen encephalitis
Westfall, J. J., Schwind, W. N., Sran, S., Navarro, J. B., Leonard, J., Pindrik, J. A., Pierson, C. R., Boué, D. R., Koboldt, D. C., Ostendorf, A. P., et al. (2022) · Figshare · doi:10.6084/m9.figshare.21601407
Additional file 2 of Rise and fall of peroxisomes during Alzheimer´s disease: a pilot study in human brains
Semikasev, E., Ahlemeyer, B., Acker, T., Schänzer, A., & Baumgart‐Vogt, E. (2024) · Figshare · doi:10.6084/m9.figshare.26588832
Additional file 4 of Single-cell RNA sequencing reveals the evolution of the immune landscape during perihematomal edema progression after intracerebral hemorrhage
Zhang, P., Gao, C., Guo, Q., Yang, D., Zhang, G., Lu, H., Zhang, L., Zhang, G., & Li, D. (2024) · Figshare · doi:10.6084/m9.figshare.26726462
Additional file 18 of Amyloid-beta and tau pathologies act synergistically to induce novel disease stage-specific microglia subtypes
Kim, D. W., Tu, K. J., Wei, A., Lau, A., Gonzalez-Gil, A., Cao, T., Braunstein, K. E., Ling, J. P., Troncoso, J. C., Wong, P. C., et al. (2024) · Figshare · doi:10.6084/m9.figshare.26555723
Additional file 1 of Alzheimer’s disease-related transcriptional sex differences in myeloid cells
Coales, I., Tsartsalis, S., Fancy, N. N., Weinert, M., Clode, D., Owen, D., & Matthews, P. (2022) · Figshare · doi:10.6084/m9.figshare.21285653
Additional file 1 of Microglia phenotypes are associated with subregional patterns of concomitant tau, amyloid-β and α-synuclein pathologies in the hippocampus of patients with Alzheimer’s disease and dementia with Lewy bodies
Fixemer, S., Ameli, C., Hammer, G. P., Salamanca, L., Huarte, O. U., Schwartz, C., Gérardy, J.-J., Mechawar, N., Skupin, A., Mittelbronn, M., et al. (2022) · Figshare · doi:10.6084/m9.figshare.19373325
Additional file 5 of Microglia phenotypes are associated with subregional patterns of concomitant tau, amyloid-β and α-synuclein pathologies in the hippocampus of patients with Alzheimer’s disease and dementia with Lewy bodies
Fixemer, S., Ameli, C., Hammer, G. P., Salamanca, L., Huarte, O. U., Schwartz, C., Gérardy, J.-J., Mechawar, N., Skupin, A., Mittelbronn, M., et al. (2022) · Figshare · doi:10.6084/m9.figshare.19373337
Additional file 5 of Molecular and spatial heterogeneity of microglia in Rasmussen encephalitis
Westfall, J. J., Schwind, W. N., Sran, S., Navarro, J. B., Leonard, J., Pindrik, J. A., Pierson, C. R., Boué, D. R., Koboldt, D. C., Ostendorf, A. P., et al. (2022) · Figshare · doi:10.6084/m9.figshare.21601434
Additional file 12 of Amyloid-beta and tau pathologies act synergistically to induce novel disease stage-specific microglia subtypes
Kim, D. W., Tu, K. J., Wei, A., Lau, A., Gonzalez-Gil, A., Cao, T., Braunstein, K. E., Ling, J. P., Troncoso, J. C., Wong, P. C., et al. (2024) · Figshare · doi:10.6084/m9.figshare.26555705
Additional file 14 of Amyloid-beta and tau pathologies act synergistically to induce novel disease stage-specific microglia subtypes
Kim, D. W., Tu, K. J., Wei, A., Lau, A., Gonzalez-Gil, A., Cao, T., Braunstein, K. E., Ling, J. P., Troncoso, J. C., Wong, P. C., et al. (2024) · Figshare · doi:10.6084/m9.figshare.26555711
Additional file 5 of Brain matters: unveiling the distinct contributions of region, age, and sex to glia diversity and CNS function
Seeker, L. A., Bestard-Cuche, N., Jäkel, S., Kazakou, N.-L., Bøstrand, S. M. K., Wagstaff, L. J., Cholewa-Waclaw, J., Kilpatrick, A. M., van Bruggen, D., Kabbe, M., et al. (2024) · Figshare · doi:10.6084/m9.figshare.26591060
Additional file 3 of Brain matters: unveiling the distinct contributions of region, age, and sex to glia diversity and CNS function
Seeker, L. A., Bestard-Cuche, N., Jäkel, S., Kazakou, N.-L., Bøstrand, S. M. K., Wagstaff, L. J., Cholewa-Waclaw, J., Kilpatrick, A. M., van Bruggen, D., Kabbe, M., et al. (2024) · Figshare · doi:10.6084/m9.figshare.26591054

Authors: Gerrits, E., Brouwer, N., Kooistra, S. M., Woodbury, M. E., Vermeiren, Y., Lambourne, M., Mulder, J., Kummer, M., Möller, T., Biber, K., Dunnen, W. F. A. D., De Deyn, P. P., Eggen, B. J. L., & Boddeke, E. W. G. M.
Affiliations: University Medical Center Groningen (NL)
AbbVie (United States) (US)
Karolinska Institutet (SE)
AbbVie (Germany) (DE)
University of Copenhagen (DK)
Corresponding author: Boddeke, Erik W. G. M.
ORCID: Gerrits, Emma
Kooistra, Susanne M.
Woodbury, Maya E.
Vermeiren, Yannick
Mulder, Jan
Kummer, Markus
Möller, Thomas
Dunnen, Wilfred F. A. den
Eggen, Bart J. L.
Boddeke, Erik W. G. M.
Venue: Acta Neuropathologica
Publisher: Springer Science and Business Media LLC
Published: 2021-02-20
Volume: 141
Issue: 5
Pages: 681-696
ISSN: 0001-6322 (ISSN-L)
1432-0533
DOI: 10.1007/s00401-021-02263-w
PMC: PMC8043951
OpenAlex: W3129453843
Cited by: 441
References: 42
Citations by year: 2026: 69 · 2025: 80 · 2024: 124 · 2023: 53 · 2022: 87 · 2021: 27
FWCI: 30.05
Type: journal article
Language: en
Open access: hybrid
doi.org
Licence: cc-by
creativecommons.org/licenses/by/4.0 (tdm)
creativecommons.org/licenses/by/4.0 (vor)
Locations: Acta Neuropathologica (publishedVersion, cc-by)
PubMed Central (publishedVersion, cc-by)
PubMed (publishedVersion)
Research at the University of Copenhagen (University of Copenhagen) (publishedVersion, cc-by)
University of Groningen research database (University of Groningen / Centre for Information Technology) (publishedVersion, cc-by)
Socio-Environmental Systems Modeling (acceptedVersion, cc-by)
University of Groningen research database (University of Groningen / Centre for Information Technology) (submittedVersion, cc-by)
Data Archiving and Networked Services (DANS) (submittedVersion, cc-by)
Funders: Rijksuniversiteit Groningen
Stichting MS Research
Fonds Wetenschappelijk Onderzoek (12Z1620N)
Universitair Medisch Centrum Groningen
Vlaamse Instelling voor Technologisch Onderzoek
Alzheimer Nederland
Vlaamse regering
Topics: Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
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
Keywords: Alzheimer's disease, microglia, amyloid plaques, tau pathology, microglial activation, microglial phenotype, single-nucleus RNA sequencing, phosphorylated tau, disease-associated microglia, microglia-targeted therapy
MeSH terms: Aged, Aged, 80 and over, Alzheimer Disease, Brain, Female, Humans, Male, Amyloid beta-Peptides, tau Proteins, Microglia

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Distinct amyloid-β and tau-associated microglia profiles in Alzheimer’s disease

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