Diverse human astrocyte and microglial transcriptional responses to Alzheimer’s pathology
Open accessPublished version of a preprint
Abstract
To better define roles that astrocytes and microglia play in Alzheimer’s disease (AD), we used single-nuclei RNA-sequencing to comprehensively characterise transcriptomes in astrocyte and microglia nuclei selectively enriched during isolation post-mortem from neuropathologically defined AD and control brains with a range of amyloid-beta and phospho-tau (pTau) pathology. Significant differences in glial gene expression (including AD risk genes expressed in both the astrocytes [ CLU , MEF2C , IQCK ] and microglia [ APOE , MS4A6A , PILRA ]) were correlated with tissue amyloid or pTau expression. The differentially expressed genes were distinct between with the two cell types and pathologies, although common (but cell-type specific) gene sets were enriched with both pathologies in each cell type. Astrocytes showed enrichment for proteostatic, inflammatory and metal ion homeostasis pathways. Pathways for phagocytosis, inflammation and proteostasis were enriched in microglia and perivascular macrophages with greater tissue amyloid, but IL1-related pathway enrichment was found specifically in association with pTau. We also found distinguishable sub-clusters in the astrocytes and microglia characterised by transcriptional signatures related to either homeostatic functions or disease pathology. Gene co-expression analyses revealed potential functional associations of soluble biomarkers of AD in astrocytes ( CLU ) and microglia ( GPNMB ). Our work highlights responses of both astrocytes and microglia for pathological protein clearance and inflammation, as well as glial transcriptional diversity in AD.
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The snRNA-seq dataset contains over 100,000 astrocyte nuclei in each brain region with ≈6,000 average total reads and ≈2,500 average total genes detected, which is orders of magnitude higher than previous studies.
“resulting in over 100,000 astrocyte nuclei in each brain region with ≈6,000 average total number of reads and ≈2,500 average total number of genes detected, which is orders of magnitude higher than previous studies9–15”
From Astrocyte transcriptomic changes along the spatiotemporal progression of Alzheimer’s disease (2024) · cites this paper as [15]
The Introduction and Results (page numbers not provided) report 52,706 astrocyte nuclei in total, not over 100,000 in each brain region. The Results give averages of 8,775 UMIs and 3,166 distinct genes per astrocyte nucleus, rather than the claimed approximately 6,000 reads and 2,500 genes. (LLM, conf=0.90)
Checked by a reasoning model — may be wrong.
Experimental — accuracy not yet measuredThe exhausted phase may have confounded previous studies that compared only control and severe AD donors or grouped late- and end-stage donors (Braak stage V/VI) together.
“may have confounded previous studies that compared only control and severe AD donors or grouped late- and end-stage donors (Braak stage V/VI) together9–15”
From Astrocyte transcriptomic changes along the spatiotemporal progression of Alzheimer’s disease (2024) · cites this paper as [15]
The Discussion (page unavailable) says categorical Braak stages do not directly reflect local tissue pathology, supporting the concern that grouping donors by stage can obscure differences. It does not identify an exhausted phase or say that such a phase may have confounded earlier control-versus-severe-AD studies or studies grouping Braak V and VI donors. (LLM, conf=0.76)
Experimental — accuracy not yet measuredIndependent snRNAseq data for microglia and astrocytes enriched by FACS sorting showed increased numbers of senescence genes upregulated in both microglia (YPEL3, IQGAP2, SQSTM1) and astrocytes (GLB1, SQSTM1, MRAS) with greater tissue β-amyloid densities.
“We found increased numbers of senescence genes upregulated in both microglia (YPEL3, IQGAP2, SQSTM1) and astrocytes (GLB1, SQSTM1, MRAS) with greater levels of tissue β-amyloid densities [66] (Supplementary Fig. 7a, b, Supplementary data S7).”
From Characterisation of premature cell senescence in Alzheimer's disease using single nuclear transcriptomics (2024) · cites this paper as [66]
No astroglial sub-population showed greater expression of the senescence gene set with AD.
“Finally, we also explored senescence pathway expression in the six astroglial sub-populations that we described previously [66], but did not find that any of these sub-populations showed greater expression of the senescence gene set with AD (Fig. 6c, d, Supplementary Fig. 10c).”
From Characterisation of premature cell senescence in Alzheimer's disease using single nuclear transcriptomics (2024) · cites this paper as [66]
The study's sample sizes are similar to those reported in previous publications.
“our sample sizes are similar to those reported in previous publications9–17”
From Astrocyte transcriptomic changes along the spatiotemporal progression of Alzheimer’s disease (2024) · cites this paper as [15]
Microglial transcripts are most highly positively associated with tissue Aβ and tissue pTau density.
“The study found that microglial transcripts were most highly positively associated with tissue Aβ and tissue pTau density.”
From Microglia in neurodegenerative diseases: mechanism and potential therapeutic targets (2023) · cites this paper as [145]
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The good, the bad, and the opportunities of the complement system in neurodegenerative disease
Schartz, N. D., & Tenner, A. J. (2020) · Journal of Neuroinflammation · doi:10.1186/s12974-020-02024-8 · Cited by 283 · cited 1× · see citing works
“Microglia may contribute to astrocyte activation through C1q expression and C1q and other complement cascade proteins co-localise with amyloid plaques in AD [50].”
BackgroundSingle-nucleus RNA-seq identifies Huntington disease astrocyte states
Al-Dalahmah, O., Sosunov, A. A., Shaik, A., Ofori, K., Liu, Y., Vonsattel, J. P., Adorjan, I., Menon, V., & Goldman, J. E. (2020) · Acta Neuropathologica Communications · doi:10.1186/s40478-020-0880-6 · Cited by 264 · see citing works
APOE and TREM2 regulate amyloid-responsive microglia in Alzheimer’s disease
Nguyen, A. T., Wang, K., Hu, G., Wang, X., Miao, Z., Azevedo, J. A., Suh, E., Van Deerlin, V. M., Choi, D., Roeder, K., et al. (2020) · Acta Neuropathologica · doi:10.1007/s00401-020-02200-3 · Cited by 241 · cited 2× · see citing works
“Our analytical approach for addressing heterogeneity in the samples also differs from most prior studies (although it is not without similar precedents [7, 41]).”
BackgroundResultSerrano-Pozo, A., Muzikansky, A., Gómez-Isla, T., Growdon, J. H., Betensky, R. A., Frosch, M. P., & Hyman, B. T. (2013) · Journal of Neuropathology & Experimental Neurology · doi:10.1097/nen.0b013e3182933788 · Cited by 226 · cited 1× · see citing works
“Activated astrocytes and microglia are found around amyloid plaques [52] and genes associated with AD risk are enriched in both cell types, particularly in microglia [12, 56].”
BackgroundKim, W.-K., Alvarez, X., Fisher, J., Bronfin, B., Westmoreland, S., McLaurin, J., & Williams, K. (2006) · The American Journal of Pathology · doi:10.2353/ajpath.2006.050215 · Cited by 225 · cited 2× · see citing works
“Clustering parameters selected to distinguish PVM [identified by markers such as CD163, MRC1 (CD206), and MSR1 [29]] also identified three clusters of nuclei (designated Micro1, 2, and 3) expressing different sets of microglial marker genes (Fig.”
BackgroundThe role of Wnt signaling in neuronal dysfunction in Alzheimer's Disease
Inestrosa, N. C., & Toledo, E. M. (2008) · Molecular Neurodegeneration · doi:10.1186/1750-1326-3-9 · Cited by 206 · see citing works
TGF-β Family Signaling in Neural and Neuronal Differentiation, Development, and FunctionPreprint
Meyers, E. A., & Kessler, J. A. (2017) · Cold Spring Harbor Perspectives in Biology · doi:10.1101/cshperspect.a022244 · Cited by 202 · see citing works
Individuals with progranulin haploinsufficiency exhibit features of neuronal ceroid lipofuscinosis
Ward, M. E., Chen, R., Huang, H.-Y., Ludwig, C., Telpoukhovskaia, M., Taubes, A., Boudin, H., Minami, S. S., Reichert, M., Albrecht, P., et al. (2017) · Science Translational Medicine · doi:10.1126/scitranslmed.aah5642 · Cited by 193 · cited 1× · see citing works
“7c,d, online resource), as well as those for genes associated with risks for other neurodegenerative disorders (LRRK2, SNCA and GPNMB, associated with Parkinson’s disease [8], and GRN, associated with ceroid lipofuscinosis [71] and frontotemporal dementia [4]).”
BackgroundVilalta, A., & Brown, G. C. (2017) · FEBS Journal · doi:10.1111/febs.14323 · Cited by 174 · cited 1× · see citing works
“By contrast, “core” or homeostatic astrocyte transcripts, such as those for glutamate transporters SLC1A3 and SLC1A2 or for IL-33 (CSF1R ligand, which promotes microglial synaptic remodelling [69]), were downregulated.”
BackgroundHüttenrauch, M., Ogorek, I., Klafki, H., Otto, M., Stadelmann, C., Weggen, S., Wiltfang, J., & Wirths, O. (2018) · Acta Neuropathologica Communications · doi:10.1186/s40478-018-0612-3 · Cited by 166 · cited 2× · see citing works
“These analyses also highlighted potential functional relationships of GPNMB (concentrations of the protein product of which are increased in brain samples and cerebrospinal fluid of sporadic AD patients [23]) with a diverse group of genes connected to transcription factors whose regulons were up-regulated with amyloid…”
BackgroundImmature excitatory neurons develop during adolescence in the human amygdala
Sorrells, S. F., Paredes, M. F., Velmeshev, D., Herranz‐Pérez, V., Sandoval, K., Mayer, S., Chang, E. F., Insausti, R., Kriegstein, A. R., Rubenstein, J. L. R., et al. (2019) · Nature Communications · doi:10.1038/s41467-019-10765-1 · Cited by 145 · cited 1× · see citing works
“MAST was used to identify genes differentially expressed (associated) with histopathological features (using pTau or amyloid-beta as markers) [14, 59] to perform zero-inflated regression analysis by fitting a mixed model.”
MethodTranscriptional profiling of microglia; current state of the art and future perspectives
Gerrits, E., Heng, Y., Boddeke, E. W. G. M., & Eggen, B. J. L. (2020) · Glia · doi:10.1002/glia.23767 · Cited by 140 · see citing works
Patir, A., Shih, B., McColl, B. W., & Freeman, T. C. (2019) · Glia · doi:10.1002/glia.23572 · Cited by 90 · see citing works
Das, S., Li, Z., Noori, A., Hyman, B. T., & Serrano-Pozo, A. (2020) · Journal of Neuroinflammation · doi:10.1186/s12974-020-01898-y · Cited by 80 · see citing works
CD74 interacts with APP and suppresses the production of Aβ
Matsuda, S., Matsuda, Y., & D'adamio, L. (2009) · Molecular Neurodegeneration · doi:10.1186/1750-1326-4-41 · Cited by 78 · see citing works
Imbalance between pro-oxidant and pro-antioxidant functions of zinc in disease
Hao, Q., & Maret, W. (2005) · Journal of Alzheimer s Disease · doi:10.3233/jad-2005-8209 · Cited by 74 · cited 1× · see citing works
“The latter proteins modulate neuroprotective superoxide dismutases through their regulation of Cu and Zn concentrations in extra- and intracellular compartments [20, 21, 54].”
BackgroundSignificance of metallothioneins in aging brain
SHARMA, S. K., & Ebadi, M. (2014) · Neurochemistry International · doi:10.1016/j.neuint.2013.12.009 · Cited by 70 · cited 1× · see citing works
“The latter proteins modulate neuroprotective superoxide dismutases through their regulation of Cu and Zn concentrations in extra- and intracellular compartments [20, 21, 54].”
BackgroundThe Chaperone Activity of Clusterin is Dependent on Glycosylation and Redox Environment
Rohne, P., Prochnow, H., Wolf, S., Renner, B., & Koch-Brandt, C. (2014) · Cellular Physiology and Biochemistry · doi:10.1159/000366365 · Cited by 68 · see citing works
Transcriptional signatures of tau and amyloid neuropathology
Castanho, I., Murray, T. K., Hannon, E., Jeffries, A., Walker, E., Laing, E., Baulf, H., Harvey, J., Bradshaw, L., Randall, A., et al. (2020) · Cell Reports · doi:10.1016/j.celrep.2020.01.063 · Cited by 62 · cited 1× · see citing works
“Our analytical approach for addressing heterogeneity in the samples also differs from most prior studies (although it is not without similar precedents [7, 41]).”
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“Both amyloid-beta and pTau pathology were associated with increased expression of genes implicated in integrin interactions with laminin and fibrillin, the APP (astrocyte)–CD74 (microglia) ligand pair, which can suppress amyloid-beta production [37], and inferred CD99 (astrocyte)–PILRA (microglia) interactions that ma…”
BackgroundBMP4 overexpression induces the upregulation of APP/Tau and memory deficits in Alzheimer’s disease
Zhang, X., Li, J., Ma, L., Xu, H., Cao, Y., Liang, W., Ma, J., Wang, Z. P., & Li, Y. (2021) · Cell Death Discovery · doi:10.1038/s41420-021-00435-x · Cited by 28 · see citing works
Roles and Therapeutic Potential of Metallothioneins in Neurodegenerative Diseases
Hozumi, I. (2013) · Current Pharmaceutical Biotechnology · doi:10.2174/1389201011314040004 · Cited by 26 · cited 1× · see citing works
“The latter proteins modulate neuroprotective superoxide dismutases through their regulation of Cu and Zn concentrations in extra- and intracellular compartments [20, 21, 54].”
BackgroundTrousse, F., Jemli, A., Silhol, M., Garrido, E., Crouzier, L., Naert, G., Maurice, T., & Rossel, M. (2019) · Brain Behavior and Immunity · doi:10.1016/j.bbi.2019.05.019 · Cited by 23 · cited 1× · see citing works
“Independent of this, amyloid-beta pathology alone was associated with higher probabilities of CXCL12 (microglial)–CXCR7 (astrocytic) interactions implicated in neurogenesis and learning [38, 66], BMP4 (microglial)–BMP1RA Fig.”
BackgroundHoltz, G. (1983) · American Journal of Obstetrics and Gynecology · doi:10.1016/0002-9378(83)91131-6 · Cited by 22 · see citing works
scFlow: A Scalable and Reproducible Analysis Pipeline for Single-Cell RNA Sequencing DataPreprint
Khozoie, C., Fancy, N. N., Marjaneh, M. M., Murphy, A. E., Matthews, P. M., & Skene, N. (2021) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2021.08.16.456499 · Cited by 21 · see citing works
Self-citationSingle nucleus sequencing fails to detect microglial activation in human tissuePreprint
Thrupp, N., Frigerio, C. S., Wolfs, L., Skene, N., Poovathingal, S., Fourne, Y., Matthews, P. M., Theys, T., Mancuso, R., Strooper, B. D., et al. (2020) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2020.04.13.035386 · Cited by 11 · cited 1× · see citing works
“Even so, the nuclear transcriptome may be biased relative to that from a whole cell, potentially reducing the power to detect some genes reported from studies of related pathologies in mouse models [64].”
BackgroundSelf-citation[Nucleic acid metabolism of hair cells and spiral ganglion cells].
Kon, I., & Ito, I. (1972) · PubMed · Cited by 6 · see citing works
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Microglia 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 · see citing works
“145 These results suggest that microglia respond to the pathology of AD.”
Neuroinflammation in Alzheimer disease
Heneka, M. T., van der Flier, W. M., Jessen, F., Hoozemanns, J., Thal, D. R., Boche, D., Brosseron, F., Teunissen, C., Zetterberg, H., Jacobs, A. H., et al. (2025) · Nature Reviews Immunology · doi:10.1038/s41577-024-01104-7 · Cited by 638 · see citing works
“Nevertheless, isolation of microglial cells from AD brains and subsequent analysis of the transcriptome has provided important insights into microglial cell activation states 220,222 .”
Nutma, E., Fancy, N. N., Weinert, M., Tsartsalis, S., Marzin, M. C., Muirhead, R. C. J., Falk, I. N., Breur, M., de Bruin, J., Hollaus, D., et al. (2023) · Nature Communications · doi:10.1038/s41467-023-40937-z · Cited by 194 · see citing works
“Quality control, sampleintegration, dimension reduction and clustering were performed using default parameters as previously described 41,83 .”
InfluentialSelf-citationDolan, 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 174 · see citing works
Human Microglia Show Unique Transcriptional Changes in Alzheimer's Disease
Prater, K. E., Green, K. J., Mamde, S., Sun, W., Cochoit, A., Smith, C. L., Chiou, K. L., Heath, L., Rose, S. E., Wiley, J., et al. (2023) · Nature Aging · doi:10.1038/s43587-023-00424-y · Cited by 164 · see citing works
Jie, F., Yang, X., Yang, B., Liu, Y., Wu, L., & Lu, B. (2022) · Biomedicine & Pharmacotherapy · doi:10.1016/j.biopha.2022.113317 · Cited by 159 · see citing works
Insights into Alzheimer’s disease from single-cell genomic approaches
Murdock, M. H., & Tsai, L.-H. (2023) · Nature Neuroscience · doi:10.1038/s41593-022-01222-2 · Cited by 148 · see citing works
“Smith et al.(134) GSE160936 12 Entorhinal and somatosensory cortex NEUN/SOX10 52,706 astrocytes and 27,592 microglia”
BackgroundAstrocyte transcriptomic changes along the spatiotemporal progression of Alzheimer’s disease
Serrano-Pozo, A., Li, H., Li, Z., Muñoz-Castro, C., Jaisa-aad, M., Healey, M. A., Welikovitch, L. A., Jayakumar, R., Bryant, A. G., Noori, A., et al. (2024) · Nature Neuroscience · doi:10.1038/s41593-024-01791-4 · Cited by 140 · see citing works
Inflammatory aspects of Alzheimer’s disease
Lucena, P. B., & Heneka, M. T. (2024) · Acta Neuropathologica · doi:10.1007/s00401-024-02790-2 · Cited by 143 · see citing works
Microglia-Astrocyte Communication in Alzheimer’s Disease
Wu, Y., & Eisel, U. L. M. (2023) · Journal of Alzheimer s Disease · doi:10.3233/jad-230199 · Cited by 118 · see citing works
“nuclei RNA-sequencing transcriptomics [167].”
Rodríguez-Giraldo, M., González-Reyes, R., Ramírez-Guerrero, S., Bonilla-Trilleras, C. E., Guardo-Maya, S., & Nava-Mesa, M. O. (2022) · International Journal of Molecular Sciences · doi:10.3390/ijms232113630 · Cited by 98 · see citing works
“Moreover, increased expression of CLU was associated with phosphorylated tau pathology in astrocytes [74].”
BackgroundInfluentialMa, Y., Deng, C., Zhou, Y., Zhang, Y., Qiu, F., Jiang, D., Zheng, G., Li, J., Shuai, J., Zhang, Y., et al. (2023) · Cell Genomics · doi:10.1016/j.xgen.2023.100383 · Cited by 107 · see citing works
Tsartsalis, S., Sleven, H., Fancy, N., Wessely, F., Smith, A. M., Willumsen, N., Cheung, T. K. D., Rokicki, M. J., Chau, V., Ifie, E., et al. (2024) · Nature Communications · doi:10.1038/s41467-024-46630-z · Cited by 95 · see citing works
“This downregulation could represent a partially adaptive response to chronically enhanced TLR signalling with AD 12 13,14 .”
Self-citationRevisiting the critical roles of reactive astrocytes in neurodegeneration
Qian, K., Jiang, X., Liu, Z., Zhang, J., Fu, P. F., Su, Y., Brazhe, N. A., Liu, D., & Zhu, L. (2023) · Molecular Psychiatry · doi:10.1038/s41380-023-02061-8 · Cited by 94 · see citing works
“Recently, the application of new methods, including snRNA-seq, has provided clues for astrocyte subset identi fi cation [135].”
MethodQian, Z., Qin, J., Lai, Y., Zhang, C., & Zhang, X. (2023) · Biomolecules · doi:10.3390/biom13040692 · Cited by 79 · see citing works
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. (2023) · Acta Neuropathologica Communications · doi:10.1186/s40478-023-01568-z · Cited by 67 · see citing works
“Human grey matter astrocytes are known to be transcriptionally heterogeneous [70, 90], but data for human white matter astrocytes is much sparser [33, 65].”
BackgroundNeurodegeneration 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 51 · see citing works
Fancy, N. N., Smith, A. M., Caramello, A., Tsartsalis, S., Davey, K., Muirhead, R. C. J., McGarry, A., Jenkyns, M. H., Schneegans, E., Chau, V., et al. (2024) · Acta Neuropathologica · doi:10.1007/s00401-024-02727-9 · Cited by 48 · see citing works
Self-citationKuntić, M., Hahad, O., Münzel, T. F., & Daiber, A. (2024) · Antioxidants · doi:10.3390/antiox13030266 · Cited by 50 · see citing works
Kim, G. S., Harmon, E., Gutierrez, M. E. C., Kim, S., Vance, L., Burrous, H., Stephenson, J. M., Chauhan, A., Banerjee, A., Wise, Z., et al. (2025) · Nature Communications · doi:10.1038/s41467-025-56847-1 · Cited by 49 · see citing works
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 · see citing works
“However, due to the relatively rarity of microglia in the brain, in this un-enriched population only a low resolution of microglia was be obtained (n = 1920 microglial nuclei compared to n = 27,592 in our enriched discovery data set [39] and n = 148,606 in the replication data set [41]).”
BackgroundMethodResultInfluentialSelf-citationRevealing cell vulnerability in Alzheimer’s disease by single-cell transcriptomics
Saura, C. A., Deprada-Fernandez, Á., Capilla-López, M. D., & Parra‐Damas, A. (2022) · Seminars in Cell and Developmental Biology · doi:10.1016/j.semcdb.2022.05.007 · Cited by 46 · see citing works
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 · see citing works
Reactive astrocytes secrete the chaperone HSPB1 to mediate neuroprotection
Yang, F., Beltran-Lobo, P., Sung, K., Goldrick, C., Croft, C. L., Nishimura, A., Hedges, E., Mahiddine, F., Troakes, C., Golde, T. E., et al. (2024) · Science Advances · doi:10.1126/sciadv.adk9884 · Cited by 46 · see citing works
“…that, in AD brain, HSPB1 is predominantly expressed in astrocytes, in line with previous immunohistochemistry studies in AD and other tauopathies, where HSPB1 expression was mostly attributed to glial cells ( 24, 63 ), and with recent single-cell transcriptomic studies in human AD brain ( 64–66 ).”
ResultHaglund, A., Zuber, V., Abouzeid, M., Yang, Y., Ko, J. H., Wiemann, L., Otero‐Jimenez, M., Muhammed, L., Feleke, R., Nott, A., et al. (2025) · Nature Genetics · doi:10.1038/s41588-024-02050-9 · Cited by 43 · see citing works
“…‘Bryois_192’ (192 total, including 105 mixed disease and 87 control cases obtained from their recent publication 7 ) and ‘MATTHEWS’ (new samples generated in-house consisting of 65 individuals split into 38 AD cases and 27 controls), a subset of which have been used in published work 26,27 .”
Self-citationCholesterol Dysmetabolism in Alzheimer’s Disease: A Starring Role for Astrocytes?
Staurenghi, E., Giannelli, S., Testa, G., Sottero, B., Leonarduzzi, G., & Gamba, P. (2021) · Antioxidants · doi:10.3390/antiox10121890 · Cited by 44 · see citing works
“Recently, an enrichment in genes involved in inflammation also emerged from the transcriptomic analysis of astrocytes from human AD brains [75].”
BackgroundKoskeridis, F., Fancy, N. N., Tan, P. F., Meena, D., Εvangelou, Ε., Elliott, P., Wang, D. Y. Q., Matthews, P. M., Dehghan, A., & Tzoulaki, I. (2024) · Nature Communications · doi:10.1038/s41467-024-53452-6 · Cited by 43 · see citing works
“…to retrieve data for single cells of the left ventricle from 6 heart failure (HF) cases and 7 healthy controls 60 , left ventricular single nuclei from 13 dilated cardiomyopathy (dCM) cases and 25 healthy controls 61 , and post-mortem brain single nuclei from 9 AD cases and 8 healthy controls 62 .”
Self-citationGalectin-3 aggravates microglial activation and tau transmission in tauopathy
Siew, J. J., Chen, H.-M., Chiu, F., Lee, C., Chang, Y., Chen, H.-L., Nguyen, T. N. A., Liao, H.-T., Liu, M., Hagar, H. C., et al. (2023) · Journal of Clinical Investigation · doi:10.1172/jci165523 · Cited by 40 · see citing works
Synapses, 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 38 · see citing works
“Indeed, single-nucleus RNAseq has demonstrated diverse astrocytic signatures in AD characterised by the enrichment of inflammatory, proteostatic genes, and metal ion homeostatic genes (Smith et al., 2021).”
BackgroundAquaporin 4 is differentially increased and dislocated in association with tau and amyloid-beta
Kecheliev, V., Boss, L., Maheshwari, U., Konietzko, U., Keller, A., Razansky, D., Nitsch, R. M., Klohs, J., & Ni, R. (2023) · Life Sciences · doi:10.1016/j.lfs.2023.121593 · Cited by 34 · see citing works
Lin, J.-P., Brake, A., Donadieu, M., Lee, A., Smith, G., Hu, K., Nair, G., Kawaguchi, R., Sati, P., Geschwind, D. H., et al. (2025) · Science · doi:10.1126/science.adp6325 · Cited by 35 · see citing works
Mosaic loss of Chromosome Y in aged human microgliaPreprint
Vermeulen, M., Pearse, R. V., Young‐Pearse, T. L., & Mostafavi, S. (2022) · Genome Research · doi:10.1101/gr.276409.121 · Cited by 33 · see citing works
“Smith et al. (2022) enriched for microglia and astrocyte nuclei from the ECs and SSCs of AD diagnosed and control donors, whereas Olah et al. (2020) and Mancuso et al. (2019) enriched for microglia from DLPFC and temporal cortex tissue, respectively.”
InfluentialLiu, Y., Tan, Y., Zhang, Z., Li, H., Yi, M., Zhang, Z., Hui, S., & Peng, W. (2022) · Ageing Research Reviews · doi:10.1016/j.arr.2022.101831 · Cited by 33 · see citing works
Sighencea, M. G., Popescu, R. Ș., & Trifu, S. C. (2024) · International Journal of Molecular Sciences · doi:10.3390/ijms252212311 · Cited by 32 · see citing works
“Indeed, astrocyte-mediated tauopathy risk loci, which encompass genes related to clustering, Myocyte Enhancer Factor 2C, and IQ Domain-Containing Protein K, have been identified in the postmortem brains of AD patients through single-nuclei RNA-sequencing transcriptomics [90].”
Lish, A. M., Ashour, N., Pearse, R. V., Galle, P. C., Orme, G. A., Heuer, S. E., Benoit, C. R., Alexander, K. D., Grogan, E. F. L., Terzioğlu, G., et al. (2025) · Cell Reports · doi:10.1016/j.celrep.2025.115777 · Cited by 29 · see citing works
“Given that AD mouse models and postmortem human AD brain tissues display upregulated DAM signatures, 4,61,62 we next investigated whether the DAM-like cluster in iMG TCs was altered in the presence of fAD neurons.”
Genetic insights into immune mechanisms of Alzheimer’s and Parkinson’s disease
Nott, A., & Holtman, I. R. (2023) · Frontiers in Immunology · doi:10.3389/fimmu.2023.1168539 · Cited by 31 · see citing works
Tarawneh, R. (2023) · Biomolecules · doi:10.3390/biom13050830 · Cited by 29 · see citing works
“Several AD risk genes are expressed in astrocytes (APOE4, WWOX, CLU, CDK2AP1, MEF2C, and IQCK) and are linked to both amyloid and tau metabolism [95,103].”
BackgroundSattarov, R., Havers, M., Orbjörn, C., Stomrud, E., Janelidze, S., Laurell, T., & Mattsson, N. (2024) · Scientific Reports · doi:10.1038/s41598-024-75406-0 · Cited by 27 · see citing works
“Microglial transcripts are associated with tissue Aβ and tau density 77 .”
BackgroundSt‐Pierre, M., VanderZwaag, J., Loewen, S. M., & Tremblay, M. (2022) · Frontiers in Cellular Neuroscience · doi:10.3389/fncel.2022.932572 · Cited by 27 · see citing works
Wang, Z., Ma, Y., Sun, Y., Tan, L., Wang, H.-F., Yu, J., & Initiative, A. D. N. (2022) · Journal of Neuroinflammation · doi:10.1186/s12974-022-02679-5 · Cited by 28 · see citing works
“However, excessive glial cell activation may be a direct pathway that causes Aβ deposition, tau pathology, and neuronal damage in AD [1, 6].”
BackgroundSt‐Pierre, M., Carrier, M., Ibáñez, F. G., Khakpour, M., Wallman, M., Parent, M., & Tremblay, M. (2023) · Journal of Neuroinflammation · doi:10.1186/s12974-023-02752-7 · Cited by 26 · see citing works
“This emerging role of astrocytes in AD is corroborated notably by genome-wide association studies highlighting several astrocytic gene variants connected with a higher risk of developing lateonset AD in humans [42, 43].”
ResultZou, D., Huang, X., Lan, Y., Pan, M., Xie, J., Huang, Q., Zeng, J., Zou, C., Pei, Z., Zou, C., et al. (2024) · Pharmacological Research · doi:10.1016/j.phrs.2024.107098 · Cited by 28 · see citing works
The cGAS−STING-mediated ROS and ferroptosis are involved in manganese neurotoxicity
Zhang, Z., Yang, J., Zhou, Q., Zhong, S., Liu, J., Zhang, X., Chang, X., & Wang, H. (2024) · Journal of Environmental Sciences · doi:10.1016/j.jes.2024.05.003 · Cited by 26 · see citing works
Neurodegenerative phagocytes mediate synaptic stripping in Neuro-HIV
Liberto, G. D., Égervári, K., Kreutzfeldt, M., Schürch, C. M., Hewer, E., Wagner, I., Pasquier, R. D., & Merkler, D. (2022) · Brain · doi:10.1093/brain/awac102 · Cited by 26 · see citing works
Microglia as a cellular target of diclofenac therapy in Alzheimer’s disease
Stopschinski, B. E., Weideman, R. A., McMahan, D., Jacob, D. A., Little, B. B., Chiang, H.-S., Saez Calveras, N., & Stuve, O. (2023) · Therapeutic Advances in Neurological Disorders · doi:10.1177/17562864231156674 · Cited by 26 · see citing works
“33,34 Taken together, further studies are needed to better understand the role of various astrocyte states in AD.”
BackgroundGlia as antigen-presenting cells in the central nervous system
Sutter, P. A., & Crocker, S. J. (2022) · Current Opinion in Neurobiology · doi:10.1016/j.conb.2022.102646 · Cited by 23 · see citing works
Hassan, H., Rawlinson, C., Lan, Y., Jenkins, S. I., & Chen, R. (2025) · Biomolecules · doi:10.3390/biom15111629 · Cited by 24 · see citing works
“However, prolonged exposure to these pathological proteins can convert microglia from a protective to a dysfunctional state, thereby contributing to AD progression [62].”
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Plasticity of human microglia and brain perivascular macrophages in aging and Alzheimer’s disease
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“The MITF network is notably enriched with markers of phagocytic activity and has been recognized as a crucial regulator of homeostatic microglial functions, particularly in promoting autophagic states and enabling microglia to migrate, detect and clear Aβ/tau proteinopathies 22,23,69–71 .”
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Ceyzériat, K., Zilli, T., Millet, P., Koutsouvelis, N., Dipasquale, G., Fossey, C., Cailly, T., Fabis, F., Frisoni, G. B., Garibotto, V., et al. (2022) · Journal of Neuroinflammation · doi:10.1186/s12974-022-02673-x · Cited by 21 · see citing works
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Self-citationProteomics of the astrocyte secretome reveals changes in their response to soluble oligomeric Aβ
Matafora, V., Gorb, A., Yang, F., Noble, W. J., Bachi, A., Perez‐Nievas, B. G., & Jiménez-Sánchez, M. (2023) · Journal of Neurochemistry · doi:10.1111/jnc.15875 · Cited by 18 · see citing works
Minding the Gap: Exploring Neuroinflammatory and Microglial Sex Differences in Alzheimer’s Disease
Reed-Geaghan, E. G., & Keller-Norrell, P. R. (2023) · International Journal of Molecular Sciences · doi:10.3390/ijms242417377 · Cited by 19 · see citing works
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“In addition, Smith et al. reported that the PILRA gene is upregulated in microglia isolated from neuropathologically defined AD brains and is correlated with Aβ and p-tau expression [96].”
Microglial apolipoprotein E particles contribute to neuronal senescence and synaptotoxicity
Wang, N., Cai, L., Pei, X., Lin, Z., Huang, L., Liang, C., Wei, M., Shao, L., Guo, T., Huang, F., et al. (2024) · iScience · doi:10.1016/j.isci.2024.110006 · Cited by 18 · see citing works
Chen, C., Lan, Z., Tang, X., Chen, W., Zhou, X. W., Su, H., Su, R., Chen, Z., Chen, H., Guo, Y., et al. (2024) · Annals of Neurology · doi:10.1002/ana.27001 · Cited by 16 · see citing works
Aghaizu, N. D., Jolly, S., Samra, S. K., Kalmár, B., Craessaerts, K., Greensmith, L., Salinas, P. C., Strooper, B. D., & Whiting, P. J. (2023) · eNeuro · doi:10.1523/eneuro.0306-22.2022 · Cited by 14 · see citing works
“In fact, numerous single-cell RNA-Seq analyses have identified gene expression signatures that differed between mouse and human DAM/ARM populations (Grubman et al., 2019; Mathys et al., 2019; Nguyen et al., 2020; Olah et al., 2020; Smith et al., 2022).”
BackgroundHe, Z., Chen, Q., Wang, K., Lin, J., Peng, Y., Zhang, J., Yan, X., & Yan, J. (2024) · European Journal of Neuroscience · doi:10.1111/ejn.16242 · Cited by 17 · see citing works
“Additionally, inflammatory pathways were significantly enriched in astrocytes, suggesting their proinflammatory role in AD progression (Smith et al., 2022).”
BackgroundSchauer, S. P., Tóth, B. I., Lee, J., Honigberg, L. A., Ramakrishnan, V., Jiang, J. Z., Kollmorgen, G., Bayfield, A., Wild, N., Hoffman, J., et al. (2024) · Alzheimer s & Dementia · doi:10.1002/alz.14346 · Cited by 17 · see citing works
“36,37 Together with the CSF YKL-40 observations, these findings were unexpected because semorinemab was developed on an IgG4 backbone, which has been demonstrated to have lower binding affinity to fragment crystallizable gamma receptor (FcR) and expected to have reduced immune effector function.”
Refining the interactions between microglia and astrocytes in Alzheimer’s disease pathology
Chen, J., Xu, S., Wang, L., Liu, X., Liu, G., Tan, Q., Li, W., Zhang, S., & Du, Y. (2025) · Neuroscience · doi:10.1016/j.neuroscience.2025.03.033 · Cited by 16 · see citing works
Mao, S., Qiao, R., Wang, Q., Shen, L., Li, D., Huo, X., Wang, J., Liu, K., Chen, W., Zhu, T., et al. (2025) · MedComm · doi:10.1002/mco2.70329 · Cited by 15 · see citing works
“Past studies have identified many AD-related risk genes expressed by astrocytes, such as APOE , SLC1A2 , CLU , MEF2C , IQCK , and so on [1, 51, 52].”
Kwon, S. H., Parthiban, S., Tippani, M., Divecha, H. R., Eagles, N. J., Lobana, J. S., Williams, S. R., Mak, M., Bharadwaj, R. A., Kleinman, J. E., et al. (2023) · GEN Biotechnology · doi:10.1089/genbio.2023.0019 · Cited by 14 · see citing works
Ma, Y., Xia, Y., Karako, K., Song, P., Tang, W., & Hu, X. (2025) · Molecular Neurobiology · doi:10.1007/s12035-025-04997-0 · Cited by 13 · see citing works
ApoE-calypse tau: ApoE–tau synergy in Alzheimer’s disease
Lennol, M. P., Bordier, C., Kamelher, L., Ulrich, J. D., Holtzman, D. M., & Gratuze, M. (2025) · The Journal of Experimental Medicine · doi:10.1084/jem.20250965 · Cited by 14 · see citing works
LRRK2 Kinase Inhibition Attenuates Astrocytic Activation in Response to Amyloid β1-42 Fibrils
Filippini, A., Salvi, V., Dattilo, V., Magri, C., Castrezzati, S., Veerhuis, R., Bosisio, D., Gennarelli, M., & Russo, I. (2023) · Biomolecules · doi:10.3390/biom13020307 · Cited by 13 · see citing works
“Given that multiple lines of evidence have indicated that amyloid‐β deposits trigger glia activation and inflammation [3,40], we investigated whether Aβ 1‐42 fibrils were able to activate primary astrocytes.”
BackgroundHu, Z., Yuan, Y.-Q., Tong, Z., Liao, M., Yuan, S., Jian, Y., Yang, J.-L., & Liu, W. (2023) · Molecular Neurobiology · doi:10.1007/s12035-023-03529-y · Cited by 13 · see citing works
MS4A superfamily molecules in tumors, Alzheimer’s and autoimmune diseases
Luo, X., Luo, B., Fei, L., Zhang, Q., Liang, X., Chen, Y., & Zhou, X. (2024) · Frontiers in Immunology · doi:10.3389/fimmu.2024.1481494 · Cited by 13 · see citing works
Liu, X., Wu, W., Li, X., Wang, C., Chai, K., Yuan, F., Zheng, H., Yao, Y., Li, C., Ye, Z., et al. (2024) · Neural Regeneration Research · doi:10.4103/nrr.nrr-d-23-01890 · Cited by 13 · see citing works
Potential of astrocytes in targeting therapy for Alzheimer’s disease
Bi, W., Lei, T., Cai, S., Zhang, X., Yang, Y., Xiao, Z., Wang, L., & Du, H. (2022) · International Immunopharmacology · doi:10.1016/j.intimp.2022.109368 · Cited by 13 · see citing works
Nutma, E., Fancy, N. N., Marzin, M. C., Tsartsalis, S., Muirhead, R. C. J., Falk, I. N., de Bruin, J., Hollaus, D., Pieterman, R., Anink, J. J., et al. (2022) · Research Square · doi:10.21203/rs.3.rs-1420033/v1 · Cited by 13 · see citing works
Self-citationTopalis, V., Voros, C., & Ziaka, M. (2025) · Journal of Geriatric Psychiatry and Neurology · doi:10.1177/08919887251361578 · Cited by 14 · see citing works
Nutma, E., Fancy, N. N., Weinert, M., Marzin, M. C., Tsartsalis, S., Muirhead, R. C. J., Falk, I. N., de Bruin, J., Hollaus, D., Pieterman, R., et al. (2022) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2022.05.11.491453 · Cited by 13 · see citing works
Self-citationJiao, H., Ge, Y., Huang, L.-Y., Liu, Y., Wu, B., Lian, P., Hao, Y., Han, S., Li, Y., Wu, K., et al. (2025) · Molecular Neurodegeneration · doi:10.1186/s13024-025-00887-0 · Cited by 11 · see citing works
Wickstead, E. S. (2023) · Biomedicines · doi:10.3390/biomedicines11082240 · Cited by 11 · see citing works
Yamakawa, M., & Rexach, J. E. (2024) · Biomedicines · doi:10.3390/biomedicines12020308 · Cited by 11 · see citing works
“The resulting microglial modules from human brain data captured reproducible states with distinct pathological associations and markers that have been validated in prior studies [9,10].”
BackgroundMethodInfluentialWei, J., Wang, M., Li, S., Han, R. F., Xu, W., Zhao, A., Yu, Q., Li, H., Li, M., & Chi, G. (2024) · Biomedicine & Pharmacotherapy · doi:10.1016/j.biopha.2024.116806 · Cited by 11 · see citing works
Associations of amyloid-β oligomers and plaques with neuropathology in the AppNL-G-F mouse
Tang, J., Huang, H., Muirhead, R., Zhou, Y., Li, J.-H., Defelice, J., Kopanitsa, M., Serneels, L., Davey, K., Tilley, B., et al. (2024) · Brain Communications · doi:10.1093/braincomms/fcae218 · Cited by 11 · see citing works
“34 This emphasizes the protective functions of astrocyte activation.”
BackgroundSelf-citationLiu, H., Tan, A. Y. S., Mehrabi, N. F., Turner, C. P., Curtis, M. A., Faull, R. L. M., Dragunow, M., Singh‐Bains, M. K., & Smith, A. M. (2024) · Neurobiology of Disease · doi:10.1016/j.nbd.2024.106749 · Cited by 11 · see citing works
Self-citationInferring gene regulatory networks by hypergraph generative model
Su, G., Wang, H., Zhang, Y., Coster, A. C., Wilkins, M. R., Cañete, P. F., Yu, D., Yang, Y., & Zhang, W. (2025) · Cell Reports Methods · doi:10.1016/j.crmeth.2025.101026 · Cited by 14 · see citing works
HDAC Inhibitors recapitulate Human Disease-Associated Microglia Signatures in vitro
Haage, V. C., Tuddenham, J. F., Bautista, A. R., Garcia, F. G., White, C. C., Patel, R., Comandante-Lou, N., Marshe, V. S., Griffin, J. K., Zhou, Y., et al. (2024) · Brain Behavior and Immunity · doi:10.1016/j.bbi.2025.05.027 · Cited by 20 · see citing works
Maksour, S., & Ooi, L. (2023) · Journal of Neurochemistry · doi:10.1111/jnc.15885 · Cited by 11 · see citing works
TSPO contributes to neuropathology and cognitive deficits in Alzheimer’s disease
Ceyzériat, K., Badina, A. M., Abjean, L., Meyer, L., Bouteldja, F., Bałkota, M., Amossé, Q., Prudhomme, O., Middleton, R. J., Liu, G.-J., et al. (2025) · Journal of Neuroinflammation · doi:10.1186/s12974-025-03583-4 · Cited by 12 · see citing works
“Genome-wide association studies (GWAS) and single-cell RNA sequencing studies strongly suggested that glial cells are causally involved in the AD pathology [6, 105–109].”
Self-citationPenning, A., Snoeck, S., Garritsen, O., Tosoni, G., Hof, A., de Boer, F., van Hasenbroek, J., Zhang, L., Thrupp, N., Craessaerts, K., et al. (2024) · Scientific Reports · doi:10.1038/s41598-024-72096-6 · Cited by 10 · see citing works
“( E ) Re-plotting of data from Smith et al. 53 showing significantly increased NACC2 expression in astrocytes in human AD brain.”
BackgroundMethodAstrocytic proteostasis in the tale of aging and neurodegeneration
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Common alterations to astrocytes across neurodegenerative disorders
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Cell-death pathways and tau-associated neuronal vulnerability in Alzheimer’s disease
Lin, G., Chancellor, S. E., Kwon, T., Woodbury, M. E., Doering, A., Abdourahman, A., Bennett, R. E., Liao, F., Pastika, T., Tamm, J. A., et al. (2025) · Cell Reports · doi:10.1016/j.celrep.2025.115758 · Cited by 13 · see citing works
Nakatsuka, N. J., Adler, D. I., Jiang, L., Hartman, A., Cheng, E., Klann, E., & Satija, R. (2025) · Nature Communications · doi:10.1038/s41467-025-62579-z · Cited by 15 · see citing works
“…et al. 96 ), GSE157827 (Lau et al. 97 ), GSE163577 (Yang et al. 98 ), GSE183068 (Sayed et al. 99 ), GSE148822 (Gerrits et al. 100 ), GSE160936 (Smith et al. 101 ), GSE167494 (Sadick et al. 102 ), GSE157783 (Smajic et al. 10 ), GSE184950 (Wang et al. 15 ), GSE193688 (Adams et al. 14 ),…”
Astrocyte transcriptomic changes along the spatiotemporal progression of Alzheimer’s diseasePreprint
Serrano‐Pozo, A., Li, Z., Woodbury, M. E., Muñoz‐Castro, C., Wachter, A., Jayakumar, R., Bryant, A. G., Noori, A., Welikovitch, L. A., Hu, M., et al. (2022) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2022.12.03.518999 · Cited by 10 · see citing works
Pomeshchik, Y., Velásquez, E., Gil, J., Klementieva, O. L., Gidlöf, R., Sydoff, M., Bagnoli, S., Nacmias, B., Sorbi, S., Westergren‐Thorsson, G., et al. (2023) · Acta Neuropathologica Communications · doi:10.1186/s40478-023-01649-z · Cited by 9 · see citing works
ATP11B Modulates Microglial Lipid Metabolism and Alleviates Alzheimer's Disease Pathology
Zhang, Y., Zhang, S., Zhao, X., Wu, P., Ying, Y., Wu, L., Zhuang, J., Chen, Z., Chao, Y., Dong, X., et al. (2025) · MedComm · doi:10.1002/mco2.70139 · Cited by 10 · see citing works
“Additionally, there was a significant decrease in the expression of Atp11b of the brain tissue of AD patients (GSE160936) (Figure 1B) [29].”
Single-nucleus multi-omics identifies shared and distinct pathways in Pick’s and Alzheimer’s disease
Shi, Z., Das, S., Morabito, S., Stocksdale, J. T., Miyoshi, E., Srinivasan, S. S., Emerson, N., Shahin, A., Rahimzadeh, N., Cao, Z., et al. (2025) · Science Advances · doi:10.1126/sciadv.ads7973 · Cited by 8 · see citing works
Mechanisms of increased Alzheimer’s disease pathology with R47H and R62H TREM2 variants
Fancy, N. N., Willumsen, N., Chau, V. M. N., Boulger, S. L., Whitwell, H. J., Wang, W., Avot, B., Thomas, M., Talbot-Martin, J., Tsartsalis, S., et al. (2026) · Acta Neuropathologica · doi:10.1007/s00401-026-03036-z · Cited by 8 · see citing works
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Recent advances in Alzheimer’s disease: From molecular mechanisms to therapeutic strategies
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Gao, W., Kong, W., Wang, S., Wen, G., & Yu, Y. (2022) · Brain Sciences · doi:10.3390/brainsci12091196 · Cited by 8 · see citing works
“Therefore, to overcome these problems and to improve the expression of gene regulatory network (GRN) inference, the integration of other data is considered to be a modified approach [5,6].”
Background
- Authors
- Smith, A. M., Davey, K., Tsartsalis, S., Khozoie, C., Fancy, N., Tang, S. S., Liaptsi, E., Weinert, M., McGarry, A., Muirhead, R. C. J., Gentleman, S., Owen, D. R., & Matthews, P. M.
- Affiliations
- Hammersmith Hospital (GB)
- University of Geneva (CH)
- Corresponding author
- Matthews, Paul M.
- ORCID
- Venue
- Acta Neuropathologica
- Published
- 2021-11-12
- Volume
- 143
- Issue
- 1
- Pages
- 75-91
- ISSN
- 0001-6322 (ISSN-L)
- 1432-0533
- PMC
- PMC8732962
- OpenAlex
- W3214651914
- Cited by
- 209
- References
- 81
- Citations by year
- 2026: 43 · 2025: 41 · 2024: 50 · 2023: 49 · 2022: 24 · 2021: 1 · 2012: 1
- FWCI
- 21.05
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Locations
- Acta Neuropathologica (publishedVersion, cc-by)
- bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion, cc-by-nc-nd)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Archive ouverte UNIGE (University of Geneva) (publishedVersion, other-oa)
- Archive ouverte UNIGE (University of Geneva) (submittedVersion, cc-by)
- Funders
- National Science Foundation
- Alzheimer's Society
- National Institute for Health and Care Research (NIHR202376, NF-SI-0514-10022)
- Parkinson's UK
- Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung (191446)
- UK Dementia Research Institute
- Medical Research Council (MR/K501013/1, MR/N008219/1, MR/M024903/1, MR/T031891/1, MR/N026934/1, MC_PC_17114)
- NIHR Imperial Biomedical Research Centre
- Topics
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Keywords
- Alzheimer's disease, astrocytes, microglia, amyloid-beta, phosphorylated tau, single-nucleus RNA sequencing, postmortem brain, apolipoprotein E, clusterin, MEF2C, MS4A6A, proteostasis, inflammation, phagocytosis, metal homeostasis, perivascular macrophages, GPNMB, gene co-expression, disease biomarkers
- MeSH terms
- Aged, Aged, 80 and over, Alzheimer Disease, Astrocytes, Brain, Female, Humans, Male, Microglia, Transcriptome
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