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Distinct amyloid-β and tau-associated microglia profiles in Alzheimer’s disease
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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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![Fig. 3 AD1-microglia subclusters gradually transition towards a phagocytic/activated profile. a UMAPs depicting trajectory analysis of homeostatic and AD1-subclusters. Color-scale indicates pseudotime, subclusters and expression of CX3CR1 (homeostasis) and MYO1E (AD1). b Density heatmaps depicting the distribution of nuclei over the UMAP for each sample group. c Violin plots depicting expression of selected genes per subcluster. *: genes significantly differentially expressed (Moran’s I test, q-value < 0.05). d Heatmap depicting all genes significantly differentially expressed over the trajectory *: Moran’s I test, q-value < 0.05). e Heatmaps depicting top 40 (non-ribosomal) DAM genes from [18] and top 37 (non-ribosomal) ARM genes from [30] over pseudotime. *: Moran’s I test, q-value < 0.05. f IBA1, P2RY12, and ITGAX co-expression in tissues from a CTR and an AD donor. Tissue core diameter = 1 mm. g Left: Microglia expressing P2RY12 and IBA1, but not ITGAX. Right: Microglia expressing IBA1 and ITGAX, but not P2RY12. Microglia are from the tissue section and exist next to each other. Scale bar = 20 μm. h Left: Gene expression of P2RY12 (green) and ITGAX (pink) along the trajectory. Right: Correlation between % P2RY12pos area and % ITGAXpos area per sample. OC Occipital Cortex; OTC Occipitotemporal Cortex; CTR non-demented controls; CTR+ non-demented controls with mild amyloid-β pathology; AD clinical and neuropathological Alzheimer’s disease; PD Parkinson’s disease; LB Lewy body dementia](/paper-figures/5d835a6601374e458c5683660903fe52/distinct-amyloid-and-tau-associated-microglia-profiles-in-alzheimers-disease-figure-3.jpg)
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“a population of clusters, namely AD1, closely reassembled the mouse DAM/MGnD phenotype, it was only abundant in human samples containing Aβ and not tau”
From Microglia and monocytes in inflammatory CNS disease: integrating phenotype and function (2022) · cites this paper as [119]
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“Together this work demonstrates, firstly, that there exist other microglial subsets in AD besides the DAM/MGnD phenotype, and secondly, that human microglia are heterogenous, thus limiting the translation of the DAM signature from animal models.”
From Microglia and monocytes in inflammatory CNS disease: integrating phenotype and function (2022) · cites this paper as [119]
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“These findings were not formally published, however two recent reports suggest the presence of B cells in the brains of patients with AD [81,82].”
From Is there a role for B cells in Alzheimer's disease? (2026) · cites this paper as [82]
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“A study using singlenucleus RNA sequencing identified a cluster of lymphocytes in AD brains enriched for the expression of IL-7R and MS4A1 genes, which encode the interleukin-7 receptor and CD20 respectively, both estab lished markers of B lymphocytes [82].”
From Is there a role for B cells in Alzheimer's disease? (2026) · cites this paper as [82]
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“There was considerable overlap between the Micro_D profile and previously reported microglial states, such as the MIMS-foamy state reported in ref. 11, amyloid-associated microglia in Alzheimer’s disease43,46,47 and lipid-associated macrophages (LAMs) in obesity48 (Extended Data Fig. 8).”
From Foamy microglia link oxylipins to disease progression in multiple sclerosis (2026) · cites this paper as [46]
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“The foamy, GPNMB+ microglial phenotype in MS lesions bears striking transcriptional similarity to LAMs in obesity, amyloid-responsive microglia in Alzheimer’s disease and foam cells in atherosclerosis18,46,48,50,51.”
From Foamy microglia link oxylipins to disease progression in multiple sclerosis (2026) · cites this paper as [46]
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“single nuclei RNA sequencing on AD brains showed that out of seven cell types, gene expression changes were shown only in microglia [119]”
From Microglia and monocytes in inflammatory CNS disease: integrating phenotype and function (2022) · cites this paper as [119]
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“AD2 did not overlap with AD1 and was more frequently observed in human brain samples showing both tau and amyloid pathology [119]”
From Microglia and monocytes in inflammatory CNS disease: integrating phenotype and function (2022) · cites this paper as [119]
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“single cell nuclei extraction from frozen human brain tissue revealed 13 distinct microglial clusters [119]”
From Microglia and monocytes in inflammatory CNS disease: integrating phenotype and function (2022) · cites this paper as [119]
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“Moreover, distinct Aβ and tau-associated microglia signatures have been discovered in AD patients.”
From Microglia in neurodegenerative diseases: mechanism and potential therapeutic targets (2023) · cites this paper as [15]
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Citations
Cites
Moderated estimation of fold change and dispersion for RNA-seq data with DESeq2
Love, M. I., Huber, W., & Anders, S. (2014) · Genome Biology · doi:10.1186/s13059-014-0550-8 · Cited by 95,106
Robinson, M. D., McCarthy, D. J., & Smyth, G. K. (2010) · Bioinformatics · doi:10.1093/bioinformatics/btp616 · Cited by 41,364
HTSeq—a Python framework to work with high-throughput sequencing data
Anders, S., Pyl, P. T., & Huber, W. (2015) · Bioinformatics · doi:10.1093/bioinformatics/btu638 · Cited by 21,464
Neuropathological stageing of Alzheimer-related changes.
Braak, H., & Braak, E. (1991) · Acta Neuropathologica · doi:10.1007/bf00308809 · Cited by 16,123
Comprehensive Integration of Single-Cell Data
Stuart, T., Butler, A., Hoffman, P., Hafemeister, C., Papalexi, E., Mauck, W. M., Hao, Y., Stoeckius, M., Smibert, P., & Satija, R. (2019) · Cell · doi:10.1016/j.cell.2019.05.031 · Cited by 15,453
A Unique Microglia Type Associated with Restricting Development of Alzheimer’s Disease
Keren-Shaul, H., Spinrad, A., Weiner, A., Matcovitch-Natan, O., Dvir-Szternfeld, R., Ulland, T. K., David, E., Baruch, K., Lara-Astaiso, D., Toth, B., et al. (2017) · Cell · doi:10.1016/j.cell.2017.05.018 · Cited by 5,493
Reversed graph embedding resolves complex single-cell trajectories
Qiu, X., Mao, Q., Tang, Y., Wang, L., Chawla, R., Pliner, H. A., & Trapnell, C. (2017) · Nature Methods · doi:10.1038/nmeth.4402 · Cited by 5,070
Buniello, A., MacArthur, J. A. L., Cerezo, M., Harris, L. W., Hayhurst, J., Malangone, C., McMahon, A., Morales, J., Mountjoy, E., Sollis, E., et al. (2019) · Nucleic Acids Research · doi:10.1093/nar/gky1120 · Cited by 4,000
Complement and microglia mediate early synapse loss in Alzheimer mouse models
Hong, S., Beja-Glasser, V. F., Nfonoyim, B. M., Frouin, A., Li, S., Ramakrishnan, S., Merry, K. M., Shi, Q., Rosenthal, A., Barres, B. A., et al. (2016) · Science · doi:10.1126/science.aad8373 · Cited by 3,343
Braak, H., Alafuzoff, I., Arzberger, T., Kretzschmar, H., & Del Tredici, K. (2006) · Acta Neuropathologica · doi:10.1007/s00401-006-0127-z · Cited by 3,172
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Microglia states and nomenclature: A field at its crossroads
Paolicelli, R. C., Sierra, A., Stevens, B., Tremblay, M.-E., Aguzzi, A., Ajami, B., Amit, I., Audinat, E., Bechmann, I., Bennett, M., et al. (2022) · Neuron · doi:10.1016/j.neuron.2022.10.020 · Cited by 1,973
Self-citationMicroglia in neurodegenerative diseases: mechanism and potential therapeutic targets
Gao, C., Jiang, J., Tan, Y., & Chen, S. (2023) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-023-01588-0 · Cited by 1,616
Microbiota–gut–brain axis and its therapeutic applications in neurodegenerative diseases
Loh, J. S., Mak, W. Q., Tan, L. K. S., Ng, C. X., Chan, H. H., Yeow, S. H., Foo, J. B., Ong, Y. S., How, C. W., & Khaw, K. Y. (2024) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-024-01743-1 · Cited by 1,193
Microglia: Immune and non-immune functions
Borst, K., Dumas, A. A., & Prinz, M. (2021) · Immunity · doi:10.1016/j.immuni.2021.09.014 · Cited by 804
hdWGCNA identifies co-expression networks in high-dimensional transcriptomics data
Morabito, S., Reese, F., Rahimzadeh, N., Miyoshi, E., & Swarup, V. (2023) · Cell Reports Methods · doi:10.1016/j.crmeth.2023.100498 · Cited by 773
ApoE in Alzheimer’s disease: pathophysiology and therapeutic strategies
Raulin, A.-C., Doss, S. V., Trottier, Z. A., Ikezu, T. C., Bu, G., & Liu, C.-C. (2022) · Molecular Neurodegeneration · doi:10.1186/s13024-022-00574-4 · Cited by 756
Microglia in Neuroinflammation and Neurodegeneration: From Understanding to Therapy
Muzio, L., Viotti, A., & Martino, G. (2021) · Frontiers in Neuroscience · doi:10.3389/fnins.2021.742065 · Cited by 581
Kamath, T., Abdulraouf, A., Burris, S. J., Langlieb, J., Gazestani, V., Nadaf, N. M., Balderrama, K., Vanderburg, C., & Macosko, E. Z. (2022) · Nature Neuroscience · doi:10.1038/s41593-022-01061-1 · Cited by 552
Human microglial state dynamics in Alzheimer’s disease progression
Sun, N., Victor, M. B., Park, Y. P., Xiong, X., Scannail, A. N., Leary, N., Prosper, S., Viswanathan, S., Luna, X., Boix, C. A., et al. (2023) · Cell · doi:10.1016/j.cell.2023.08.037 · Cited by 462
Sadick, J. S., O’Dea, M. R., Hasel, P., Dykstra, T., Faustin, A., & Liddelow, S. A. (2022) · Neuron · doi:10.1016/j.neuron.2022.03.008 · Cited by 415
Integrated multimodal cell atlas of Alzheimer’s disease
Gabitto, M. I., Travaglini, K. J., Rachleff, V. M., Kaplan, E. S., Long, B., Ariza, J., Ding, Y., Mahoney, J. T., Dee, N., Goldy, J., et al. (2024) · Nature Neuroscience · doi:10.1038/s41593-024-01774-5 · Cited by 397
Microglia in Alzheimer's disease at single-cell level. Are there common patterns in humans and mice?
Chen, Y., & Colonna, M. (2021) · Journal of Experimental Medicine · doi:10.1084/jem.20202717 · Cited by 339
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Wang, C., Zong, S., Cui, X., Wang, X., Wu, S., Wang, L., Liu, Y., & Lu, Z. (2023) · Frontiers in Immunology · doi:10.3389/fimmu.2023.1117172 · Cited by 331
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Smith, A. M., Davey, K., Tsartsalis, S., Khozoie, C., Fancy, N., Tang, S. S., Liaptsi, E., Weinert, M., McGarry, A., Muirhead, R. C. J., et al. (2022) · Acta Neuropathologica · doi:10.1007/s00401-021-02372-6 · Cited by 209
“We confirmed that transcripts positively differentially expressed in microglia were significantly enriched in nuclei with human AD pathology in previously published snRNASeq studies [16, 18, 36, 76] (Supplementary Table 3, online resource).”
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Green, G. S., Fujita, M., Yang, H.-S., Taga, M., Cain, A., McCabe, C., Comandante-Lou, N., White, C. C., Schmidtner, A. K., Zeng, L., et al. (2024) · Nature · doi:10.1038/s41586-024-07871-6 · Cited by 204
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Choi, I., Wang, M., Yoo, S., Xu, P., Seegobin, S. P., Li, X., Han, X., Wang, Q., Peng, J., Zhang, B., et al. (2023) · Nature Cell Biology · doi:10.1038/s41556-023-01158-0 · Cited by 202
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Dolan, M.-J., Therrien, M., Jereb, S., Kamath, T., Gazestani, V., Atkeson, T., Marsh, S. E., Goeva, A., Lojek, N. M., Murphy, S., et al. (2023) · Nature Immunology · doi:10.1038/s41590-023-01558-2 · Cited by 185
Sabogal-Guáqueta, A. M., Marmolejo-Garza, A., Trombetta-Lima, M., Oun, A., Hunneman, J., Chen, T., Koıstınaho, J., Lehtonen, Š., Kortholt, A., Wolters, J. C., et al. (2023) · Nature Communications · doi:10.1038/s41467-023-42096-7 · Cited by 180
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Yin, Z., Herron, S., Silveira, S., Kleemann, K., Gauthier, C., Mallah, D., Cheng, Y., Margeta, M. A., Pitts, K. M., Barry, J.-L., et al. (2023) · Nature Neuroscience · doi:10.1038/s41593-023-01355-y · Cited by 120
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Rosenzweig, N., Kleemann, K. L., Rust, T., Carpenter, M., Grucci, M., Aronchik, M., Brouwer, N., Valenbreder, I., Cooper-Hohn, J., Iyer, M., et al. (2024) · Nature Medicine · doi:10.1038/s41591-024-03122-3 · Cited by 90
Self-citationGerrits, E., Giannini, L. A. A., Brouwer, N., Melhem, S., Seilhean, D., Le Ber, I., The Brainbank Neuro-CEB Neuropathology Network, Kamermans, A., Kooij, G., de Vries, H. E., et al. (2022) · Nature Neuroscience · doi:10.1038/s41593-022-01124-3 · Cited by 88
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Bryant, A. G., Li, Z., Jayakumar, R., Serrano‐Pozo, A., Woost, B., Hu, M., Woodbury, M. E., Wachter, A., Lin, G., Kwon, T., et al. (2023) · Journal of Neuroscience · doi:10.1523/jneurosci.0237-23.2023 · Cited by 84
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Self-citationLodder, C., Scheyltjens, I., Stancu, I., Lucena, P. B., de Ravé, M. G., Vanherle, S., Vanmierlo, T., Cremers, N., Vanrusselt, H., Brône, B., et al. (2021) · Acta Neuropathologica Communications · doi:10.1186/s40478-021-01204-8 · Cited by 71
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Self-citationXu, Y., Au, N. P. B., & Ma, C. H. E. (2022) · Frontiers in Aging Neuroscience · doi:10.3389/fnagi.2022.896852 · Cited by 68
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Rauchmann, B., Brendel, M., Franzmeier, N., Trappmann, L., Zaganjori, M., Ersoezlue, E., Morenas‐Rodriguez, E., Guersel, S., Burow, L., Kurz, C., et al. (2022) · Annals of Neurology · doi:10.1002/ana.26465 · Cited by 61
“Within the microglia population, two distinct expression profiles were recently identified, associated with either Aβ load or tissue phosphorylated tau (ptau).(11) Colocalization of tau and activated microglia was demonstrated,(12,13) and Aβ plaque-dependent microglia was identified.”
Towards PET imaging of the dynamic phenotypes of microglia
Beaino, W., Janssen, B., Vugts, D. J., de Vries, H. E., & Windhorst, A. D. (2021) · Clinical & Experimental Immunology · doi:10.1111/cei.13649 · Cited by 63
Wang, Z., Liu, J., Han, J., Zhang, T., Li, S., Hou, Y., Su, H., Han, F., & Zhang, C. (2024) · Journal of Neuroinflammation · doi:10.1186/s12974-024-03166-9 · Cited by 60
Microglia Heterogeneity in Alzheimer’s Disease: Insights From Single-Cell Technologies
Wang, H. (2021) · Frontiers in Synaptic Neuroscience · doi:10.3389/fnsyn.2021.773590 · Cited by 62
Patel, T., Carnwath, T., Wang, X., Allen, M., Lincoln, S., Lewis‐Tuffin, L. J., Quicksall, Z., Lin, S., Tutor‐New, F. Q., Ho, C. C. G., et al. (2022) · Aging Cell · doi:10.1111/acel.13606 · Cited by 61
Cell type-specific changes identified by single-cell transcriptomics in Alzheimer’s disease
Luquez, T., Gaur, P., Kosater, I. M., Lam, M., Lee, D. I., Mares, J. A., Paryani, F., Yadav, A., & Menon, V. (2022) · Genome Medicine · doi:10.1186/s13073-022-01136-5 · Cited by 64
Majerníková, N., den Dunnen, W. F. A., & Dolga, A. M. (2021) · Frontiers in Aging Neuroscience · doi:10.3389/fnagi.2021.745046 · Cited by 56
Self-citationExperimental animal models of chronic inflammation
Rafiyan, M., Sadeghmousavi, S., Akbarzadehmoallemkolaei, M., & Rezaei, N. (2023) · Current Research in Immunology · doi:10.1016/j.crimmu.2023.100063 · Cited by 54
Ferroptosis mechanism and Alzheimer's disease
Feng, L., Sun, J. J., Xia, L., Shi, Q., Hou, Y., Zhang, L., Li, M., Fan, C., & Sun, B. (2023) · Neural Regeneration Research · doi:10.4103/1673-5374.389362 · Cited by 56
Podleśny-Drabiniok, A., Novikova, G., Liu, Y., Dunst, J., Temizer, R., Giannarelli, C., Marro, S., Kreslavsky, T., Marcora, E., & Goate, A. M. (2024) · Nature Communications · doi:10.1038/s41467-024-46315-7 · Cited by 52
Harnessing human iPSC-microglia for CNS-wide delivery of disease-modifying proteins
Chadarevian, J. P., Davtyan, H., Chadarevian, A. L., Nguyen, J., Capocchi, J. K., Le, L., Escobar, A., Chadarevian, T., Mansour, K., Deynega, E., et al. (2025) · Cell Stem Cell · doi:10.1016/j.stem.2025.03.009 · Cited by 60
Green, G. S., Yang, H., Fujita, M., Taga, M., Regev, A., Menon, V., Bennett, D. A. A., Habib, N., & De Jager, P. L. (2023) · Alzheimer's & Dementia · doi:10.1002/alz.083212 · Cited by 51
Neurodegeneration cell per cell
Balusu, S., Praschberger, R., Lauwers, E., Strooper, B. D., & Verstreken, P. (2023) · Neuron · doi:10.1016/j.neuron.2023.01.016 · Cited by 53
The multiple faces of extracellular vesicles released by microglia: Where are we 10 years after?
Gabrielli, M., Raffaele, S., Fumagalli, M., & Verderio, C. (2022) · Frontiers in Cellular Neuroscience · doi:10.3389/fncel.2022.984690 · Cited by 55
Tracking cell-type-specific temporal dynamics in human and mouse brains
Lu, Z., Zhang, M., Lee, J., Sziraki, A., Anderson, S., Zhang, Z., Xu, Z., Jiang, W., Ge, S., Nelson, P. T., et al. (2023) · Cell · doi:10.1016/j.cell.2023.08.042 · Cited by 51
Kuntić, M., Hahad, O., Münzel, T. F., & Daiber, A. (2024) · Antioxidants · doi:10.3390/antiox13030266 · Cited by 53
İş, Ö., Wang, X., Reddy, J. S., Min, Y., Yılmaz, E., Bhattarai, P., Patel, T., Bergman, J., Quicksall, Z., Heckman, M. G., et al. (2024) · Nature Communications · doi:10.1038/s41467-024-48926-6 · Cited by 55
Alzheimer’s disease-related transcriptional sex differences in myeloid cells
Coales, I., Tsartsalis, S., Fancy, N., Weinert, M., Clode, D., Owen, D., & Matthews, P. M. (2022) · Journal of Neuroinflammation · doi:10.1186/s12974-022-02604-w · Cited by 49
Repeated head trauma causes neuron loss and inflammation in young athletes
Butler, M. L. M. D., Pervaiz, N., Breen, K., Calderazzo, S. M., Ypsilantis, P., Wang, Y., Breda, J. C., Mazzilli, S. A., Nicks, R., Spurlock, E., et al. (2025) · Nature · doi:10.1038/s41586-025-09534-6 · Cited by 57
Microglia in Health and Diseases: Integrative Hubs of the Central Nervous System (CNS)
Sierra, A., Miron, V. E., Paolicelli, R. C., & Ransohoff, R. M. (2024) · Cold Spring Harbor Perspectives in Biology · doi:10.1101/cshperspect.a041366 · Cited by 47
Identification of distinct and age‐dependent p16High microglia subtypes
Talma, N., Gerrits, E., Wang, B., Eggen, B. J. L., & Demaria, M. (2021) · Aging Cell · doi:10.1111/acel.13450 · Cited by 46
Self-citationOverlapping Neuroimmune Mechanisms and Therapeutic Targets in Neurodegenerative Disorders
Marchi, F. D., Munitić, I., Vidatic, L., Papić, E., Rački, V., Nimac, J., Jurak, I., Novotni, G., Rogelj, B., Vuletić, V., et al. (2023) · Biomedicines · doi:10.3390/biomedicines11102793 · Cited by 47
Rao, A. T., Chen, N., Kim, M. J., Blumenfeld, J. R., Yip, O., Liang, Z., Shostak, D. M., Hao, Y., Nelson, M. R., Koutsodendris, N., et al. (2024) · Cell stem cell · doi:10.1016/j.stem.2024.10.005 · Cited by 48
Central Nervous System Macrophages in Health and Disease
Hove, H. V., Feo, D. D., Greter, M., & Becher, B. (2025) · Annual Review of Immunology · doi:10.1146/annurev-immunol-082423-041334 · Cited by 53
Das, S., Li, Z., Wachter, A., Alla, S., Noori, A., Abdourahman, A., Tamm, J. A., Woodbury, M. E., Talanian, R. V., Biber, K., et al. (2024) · Alzheimer's & Dementia · doi:10.1002/alz.13387 · Cited by 46
Self-citationShi, H., Yin, Z., Koronyo, Y., Fuchs, D.-T. S., Sheyn, J., Davis, M. R., Wilson, J. W., Margeta, M. A., Pitts, K. M., Herron, S., et al. (2022) · Acta Neuropathologica Communications · doi:10.1186/s40478-022-01439-z · Cited by 45
Zhang, P., Gao, C., Guo, Q., Yang, D., Zhang, G., Lü, H., Zhang, L., Zhang, G., & Li, D. (2024) · Journal of Neuroinflammation · doi:10.1186/s12974-024-03113-8 · Cited by 44
Gao, C., Shen, X., Tan, Y., & Chen, S. (2022) · Journal of Neuroinflammation · doi:10.1186/s12974-022-02580-1 · Cited by 48
An emerging role for microglia in stress‐effects on memory
Sanguino‐Gómez, J., Buurstede, J. C., Abiega, O., Fitzsimons, C. P., Lucassen, P. J., Eggen, B. J. L., Lesuis, S. L., Meijer, O. C., & Krugers, H. J. (2021) · European Journal of Neuroscience · doi:10.1111/ejn.15188 · Cited by 43
Self-citationBouvier, D. S., Fixemer, S., Heurtaux, T., Jeannelle, F., Frauenknecht, K. B. M., & Mittelbronn, M. G. A. (2022) · Frontiers in Physiology · doi:10.3389/fphys.2022.814889 · Cited by 43
Muñoz-Castro, C., Noori, A., Magdamo, C. G., Li, Z., Marks, J. D., Frosch, M. P., Das, S., Hyman, B. T., & Serrano-Pozo, A. (2022) · Journal of Neuroinflammation · doi:10.1186/s12974-022-02383-4 · Cited by 41
Qiu, Y., Hou, Y., Gohel, D., Zhou, Y., Xu, J., Bykova, M., Yang, Y., Leverenz, J. B., Pieper, A. A., Nussinov, R., et al. (2024) · Cell Reports · doi:10.1016/j.celrep.2024.114128 · Cited by 40
Ardura-Fabregat, A., Bosch, L. F. P., Wogram, E., Mossad, O., Sankowski, R., Aktories, P., Kieger, L., Cook, J., Hasavci, D., Ulupinar, H., et al. (2025) · Nature Neuroscience · doi:10.1038/s41593-025-02006-0 · Cited by 42
Zhou, Y., Xu, J., Hou, Y., Bekris, L., Leverenz, J. B., Pieper, A. A., Cummings, J., & Cheng, F. (2022) · Alzheimer's & Dementia: Translational Research & Clinical Interventions · doi:10.1002/trc2.12350 · Cited by 39
Multimodal Omics Approaches to Aging and Age-Related Diseases
Ji, Q., Jiang, X., Wang, M., Xin, Z., Zhang, W., Qu, J. T., & Liu, G. (2024) · Phenomics · doi:10.1007/s43657-023-00125-x · Cited by 39
Monocyte-derived macrophages act as reinforcements when microglia fall short in Alzheimer’s disease
Abellanas, M. A., Purnapatre, M., Burgaletto, C., & Schwartz, M. (2025) · Nature Neuroscience · doi:10.1038/s41593-024-01847-5 · Cited by 40
Utilising Induced Pluripotent Stem Cells in Neurodegenerative Disease Research: Focus on Glia
Albert, K., Niskanen, J., Kälvälä, S., & Lehtonen, Š. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms22094334 · Cited by 40
Spatially resolved gene signatures of white matter lesion progression in multiple sclerosis
Alsema, A. M., Wijering, M. H. C., Miedema, A., Kotah, J. M., Koster, M., Rijnsburger, M., van Weering, H. R. J., de Vries, H. E., Baron, W., Kooistra, S. M., et al. (2024) · Nature Neuroscience · doi:10.1038/s41593-024-01765-6 · Cited by 38
Self-citationSynapses, Microglia, and Lipids in Alzheimer’s Disease
Paasila, P. J., Aramideh, J. A., Sutherland, G. T., & Graeber, M. B. (2022) · Frontiers in Neuroscience · doi:10.3389/fnins.2021.778822 · Cited by 40
The Roles of Tetramethylpyrazine During Neurodegenerative Disease
Meng, Z., Chen, H., & Meng, S. (2021) · Neurotoxicity Research · doi:10.1007/s12640-021-00398-y · Cited by 37
Decoding Aging Hallmarks at the Single-Cell Level
Ma, S., Chi, X., Cai, Y., Ji, Z., Wang, S., Ren, J., & Liu, G. (2023) · Annual Review of Biomedical Data Science · doi:10.1146/annurev-biodatasci-020722-120642 · Cited by 37
Microglial phagocytosis in Alzheimer disease
Brown, G. C., St George-Hyslop, P., Paolicelli, R. C., & Lemke, G. (2026) · Nature Reviews Neurology · doi:10.1038/s41582-025-01162-y · Cited by 36
Metadata
- 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
- Venue
- Acta Neuropathologica
- Published
- 2021-02-20
- Volume
- 141
- Issue
- 5
- Pages
- 681-696
- ISSN
- 0001-6322 (ISSN-L)
- 1432-0533
- 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
- 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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