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Cited by 77Alzheimer's disease research and treatmentsNeuroinflammation and Neurodegeneration MechanismsSingle-cell and spatial transcriptomics

Human Alzheimer’s disease reactive astrocytes exhibit a loss of homeostastic gene expression

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Dai, David L., Li, Mingyao, Lee, Edward B.·2023·Acta Neuropathologica Communications
DOI 10.1186/s40478-023-01624-8PMC PMC10398957
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Abstract

Astrocytes are one of the brain’s major cell types and are responsible for maintaining neuronal homeostasis via regulating the extracellular environment, providing metabolic support, and modulating synaptic activity. In neurodegenerative diseases, such as Alzheimer’s disease, astrocytes can take on a hypertrophic appearance. These reactive astrocytes are canonically associated with increases in cytoskeletal proteins, such as glial fibrillary acidic protein and vimentin. However, the molecular alterations that characterize astrocytes in human disease tissues have not been extensively studied with single cell resolution. Using single nucleus RNA sequencing data from normal, pathologic aging, and Alzheimer’s disease brains, we identified the transcriptomic changes associated with reactive astrocytes. Deep learning-based clustering algorithms denoised expression data for 17,012 genes and clustered 15,529 astrocyte nuclei, identifying protoplasmic, gray matter and fibrous, white matter astrocyte clusters. RNA trajectory analyses revealed a spectrum of reactivity within protoplasmic astrocytes characterized by a modest increase of reactive genes and a marked decrease in homeostatic genes. Amyloid but not tau pathology correlated with astrocyte reactivity. To identify reactivity-associated genes, linear regressions of gene expression versus reactivity were used to identify the top 52 upregulated and 144 downregulated genes. Gene Ontology analysis revealed that upregulated genes were associated with cellular growth, responses to metal ions, inflammation, and proteostasis. Downregulated genes were involved in cellular interactions, neuronal development, ERBB signaling, and synapse regulation. Transcription factors were significantly enriched among the downregulated genes. Using co-immunofluorescence staining of Alzheimer’s disease brain tissues, we confirmed pathologic downregulation of ERBB4 and transcription factor NFIA in reactive astrocytes. Our findings reveal that protoplasmic, gray matter astrocytes in Alzheimer’s disease exist within a spectrum of reactivity that is marked by a strong loss of normal function.

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  1. [5]Blake JA Baldarelli R Kadin JA Richardson JE Smith CL Bult CJ Mouse genome database (MGD): knowledgebase for mouse–human comparative biology Nucleic Acids Res 2021 49 D981 D987 10.1093/nar/gkaa1083 33231642 PMC7779030 · DOI · Paper page
  2. [6]Bonneh-Barkay D Wang G Starkey A Hamilton RL Wiley CA In vivo CHI3L1 (YKL-40) expression in astrocytes in acute and chronic neurological diseases J Neuroinflamm 2010 10.1186/1742-2094-7-34 PMC2892443 20540736 · DOI
  3. [7]Bugiani M Plug BC Man JHK Breur M van der Knaap MS Heterogeneity of white matter astrocytes in the human brain Acta Neuropathol 2022 143 159 177 10.1007/s00401-021-02391-3 34878591 · DOI
  4. [8]Burda JE O’Shea TM Ao Y Suresh KB Wang S Bernstein AM Chandra A Deverasetty S Kawaguchi R Kim JH McCallum S Rogers A Wahane S Sofroniew MV Divergent transcriptional regulation of astrocyte reactivity across disorders Nature 2022 606 557 564 10.1038/s41586-022-04739-5 35614216 PMC10027402 · DOI · Paper page
  5. [9]Caiazzo M Giannelli S Valente P Lignani G Carissimo A Sessa A Colasante G Bartolomeo R Massimino L Ferroni S Settembre C Benfenati F Broccoli V Direct conversion of fibroblasts into functional astrocytes by defined transcription factors Stem Cell Rep 2015 4 25 36 10.1016/j.stemcr.2014.12.002 PMC4297873 25556566 · DOI
  6. [10]Caltagarone J Jing Z Bowser R Focal adhesions regulate Aβ signaling and cell death in Alzheimer’s disease Biochim Biophys Acta Mol Basis Dis 2007 1772 438 445 10.1016/j.bbadis.2006.11.007 PMC1876750 17215111 · DOI · Paper page
  7. [11]Canals I Ginisty A Quist E Timmerman R Fritze J Miskinyte G Monni E Hansen MG Hidalgo I Bryder D Bengzon J Ahlenius H Rapid and efficient induction of functional astrocytes from human pluripotent stem cells Nat Methods 2018 15 693 696 10.1038/s41592-018-0103-2 30127505 · DOI
  8. [12]Chen J He W Hu X Shen Y Cao J Wei Z Luan Y He L Jiang F Tao Y A role for erbb signaling in the induction of reactive astrogliosis Cell Discov 2017 10.1038/celldisc.2017.44 29238610 PMC5717352 · DOI
  9. [15]Connolly K Lehoux M O’Rourke R Assetta B Erdemir GA Elias JA Lee CG Huang YWA Potential role of chitinase-3-like protein 1 (CHI3L1/YKL-40) in neurodegeneration and Alzheimer’s disease Alzheimer’s Dement 2023 19 9 24 10.1002/ALZ.12612 35234337 PMC9437141 · DOI
  10. [16]Das S Li Z Noori A Hyman BT Serrano-Pozo A Meta-analysis of mouse transcriptomic studies supports a context-dependent astrocyte reaction in acute CNS injury versus neurodegeneration J Neuroinflamm 2020 10.1186/s12974-020-01898-y PMC7393869 32736565 · DOI · Paper page
  11. [17]Decker Y Németh E Schomburg R Chemla A Fülöp L Menger MD Liu Y Fassbender K Decreased pH in the aging brain and Alzheimer’s disease Neurobiol Aging 2021 101 40 49 10.1016/j.neurobiolaging.2020.12.007 33578193 · DOI
  12. [18]Deng Y Song H Xiao Y Zhao Y Chu L Ding J Shen X Qi X High-throughput sequencing to investigate lncRNA-circRNA-miRNA-mRNA networks underlying the effects of beta-amyloid peptide and senescence on astrocytes Front Genet 2022 10.3389/fgene.2022.868856 35646066 PMC9133720 · DOI
  13. [19]De Bastiani MA Bellaver B Brum WS Souza DG Ferreira PCL Rocha AS Povala G Ferrari-Souza JP Benedet AL Ashton NJ Karikari TK Zetterberg H Blennow K Rosa-Neto P Pascoal TA Zimmer ER Hippocampal GFAP-positive astrocyte responses to amyloid and tau pathologies Brain Behav Immun 2023 110 175 184 10.1016/j.bbi.2023.03.001 36878332 · DOI · Paper page
  14. [21]Dickson DW Farlo J Davies P Crystal H Fuld P Yen S-HC Alzheimer’s disease a double-labeling immunohistochemical study of senile plaques Am J Pathol 1988 132 1 86 2456021 PMC1880629
  15. [22]Dolfe L Tambaro S Tigro H Del Campo M Hoozemans JJM Wiehager B Graff C Winblad B Ankarcrona M Kaldmäe M Teunissen CE Rönnbäck A Johansson J Presto J The Bri2 and Bri3 BRICHOS domains interact differently with Aβ42 and Alzheimer amyloid plaques J Alzheimers Dis Rep 2018 2 27 39 10.3233/adr-170051 30480246 PMC6159705 · DOI
  16. [23]Duffy PE Rapport M Graf L Glial fibrillary acidic protein and Alzheimer-type senile dementia Neurology 1980 10.1212/WNL.30.7.778 7190246 · DOI
  17. [24]Endo F Kasai A Soto JS Yu X Qu Z Hashimoto H Gradinaru V Kawaguchi R Khakh BS Molecular basis of astrocyte diversity and morphology across the CNS in health and disease Science 1979 10.1126/science.adc9020 PMC9873482 36378959 · DOI · Paper page
  18. [26]Falcone C Martínez-Cerdeño V Astrocyte evolution and human specificity Neural Regen Res 2023 18 131 132 10.4103/1673-5374.340405 35799529 PMC9241407 · DOI
  19. [27]Gomez AM Traunmüller L Scheiffele P Neurexins: molecular codes for shaping neuronal synapses Nat Rev Neurosci 2021 22 3 137 151 10.1038/s41583-020-00415-7 33420412 PMC7612283 · DOI
  20. [29]Habib N McCabe C Medina S Varshavsky M Kitsberg D Dvir-Szternfeld R Green G Dionne D Nguyen L Marshall JL Chen F Zhang F Kaplan T Regev A Schwartz M Disease-associated astrocytes in Alzheimer’s disease and aging Nat Neurosci 2020 23 701 706 10.1038/s41593-020-0624-8 32341542 PMC9262034 · DOI · Paper page
  21. [31]Huang AYS Woo J Sardar D Lozzi B Bosquez Huerta NA Lin CCJ Felice D Jain A Paulucci-Holthauzen A Deneen B Region-specific transcriptional control of astrocyte function oversees local circuit activities Neuron 2020 106 992 1008.e9 10.1016/j.neuron.2020.03.025 32320644 PMC7879989 · DOI
  22. [32]Jiwaji Z Tiwari SS Avilés-Reyes RX Hooley M Hampton D Torvell M Johnson DA McQueen J Baxter P Sabari-Sankar K Qiu J He X Fowler J Febery J Gregory J Rose J Tulloch J Loan J Story D McDade K Smith AM Greer P Ball M Kind PC Matthews PM Smith C Dando O Spires-Jones TL Johnson JA Chandran S Hardingham GE Reactive astrocytes acquire neuroprotective as well as deleterious signatures in response to Tau and Aß pathology Nat Commun 2022 10.1038/s41467-021-27702-w 35013236 PMC8748982 · DOI · Paper page
  23. [34]Journiac N Jolly S Jarvis C Gautheron V Rogard M Trembleau A Blondeau J-P Mariani J Atrice Vernet-Der Garabedian B The nuclear receptor ROR exerts a bi-directional regulation of IL-6 in resting and reactive astrocytes Proc Natl Acad Sci 2009 106 50 21365 10.1073/pnas.0911782106 19955433 PMC2795519 · DOI
  24. [35]Köhler S Winkler U Hirrlinger J Heterogeneity of astrocytes in grey and white matter Neurochem Res 2021 46 3 14 10.1007/s11064-019-02926-x 31797158 · DOI · Paper page
  25. [37]Lakkis J Wang D Zhang Y Hu G Wang K Pan H Ungar L Reilly MP Li X Li M A joint deep learning model enables simultaneous batch effect correction, denoising, and clustering in single-cell transcriptomics Genome Res 2021 31 1753 1766 10.1101/gr.271874.120 34035047 PMC8494213 · DOI
  26. [38]Lambert SA Jolma A Campitelli LF Das PK Yin Y Albu M Chen X Taipale J Hughes TR Weirauch MT The human transcription factors Cell 2018 172 650 665 10.1016/j.cell.2018.01.029 29425488 PMC12908702 · DOI · Paper page
  27. [39]Laug D Huang TW Bosquez Huerta NA Huang AYS Sardar D Ortiz-Guzman J Carlson JC Arenkiel BR Kuo CT Mohila CA Glasgow SM Lee HK Deneen B Nuclear factor I-A regulates diverse reactive astrocyte responses after CNS injury J Clin Investig 2019 129 4408 4418 10.1172/JCI127492 31498149 PMC6763246 · DOI
  28. [40]Leng F Edison P Neuroinflammation and microglial activation in Alzheimer disease: where do we go from here? Nat Rev Neurol 2021 17 157 172 10.1038/s41582-020-00435-y 33318676 · DOI · Paper page
  29. [41]Leng K Li E Eser R Piergies A Sit R Tan M Neff N Li SH Rodriguez RD Suemoto CK Leite REP Ehrenberg AJ Pasqualucci CA Seeley WW Spina S Heinsen H Grinberg LT Kampmann M Molecular characterization of selectively vulnerable neurons in Alzheimer’s disease Nat Neurosci 2021 10.1038/s41593-020-00764-7 33432193 PMC7854528 · DOI · Paper page
  30. [42]Li Y Fan T Li X Liu L Mao F Li Y Miao Z Zeng C Song W Pan J Zhou S Wang H Wang Y Sun ZS Npas3 deficiency impairs cortical astrogenesis and induces autistic-like behaviors Cell Rep 2022 10.1016/j.celrep.2022.111289 36044858 · DOI
  31. [43]Liddelow SA Barres BA Reactive astrocytes: production, function, and therapeutic potential Immunity 2017 46 957 967 10.1016/j.immuni.2017.06.006 28636962 · DOI · Paper page
  32. [45]Lundgaard I Osório MJ Kress BT Sanggaard S Nedergaard M White matter astrocytes in health and disease Neuroscience 2014 276 161 173 10.1016/j.neuroscience.2013.10.050 24231735 PMC4016995 · DOI
  33. [46]Mandybur TI Chuirazzi CC Astrocytes and the plaques of Alzheimer’s disease Neurology 1990 10.1212/WNL.40.4.635 1690867 · DOI
  34. [47]Mathys H Davila-Velderrain J Peng Z Gao F Mohammadi S Young JZ Menon M He L Abdurrob F Jiang X Martorell AJ Ransohoff RM Hafler BP Bennett DA Kellis M Tsai LH Single-cell transcriptomic analysis of Alzheimer’s disease Nature 2019 570 332 337 10.1038/s41586-019-1195-2 31042697 PMC6865822 · DOI · Paper page
  35. [48]Matos M Augusto E Oliveira CR Agostinho P Amyloid-beta peptide decreases glutamate uptake in cultured astrocytes: involvement of oxidative stress and mitogen-activated protein kinase cascades Neuroscience 2008 156 898 910 10.1016/j.neuroscience.2008.08.022 18790019 · DOI
  36. [49]Medeiros de Araújo JA Barão S Mateos-White I Espinosa A Costa MR Gil-Sanz C Müller U ZBTB20 is crucial for the specification of a subset of callosal projection neurons and astrocytes in the mammalian neocortex Development 2021 10.1242/dev.196642 34351428 PMC8406536 · DOI
  37. [52]Olabarria M Noristani HN Verkhratsky A Rodríguez JJ Concomitant astroglial atrophy and astrogliosis in a triple transgenic animal model of Alzheimer’s disease Glia 2010 58 831 838 10.1002/glia.20967 20140958 · DOI · Paper page
  38. [53]Orre M Kamphuis W Osborn LM Jansen AHP Kooijman L Bossers K Hol EM Isolation of glia from Alzheimer’s mice reveals inflammation anddysfunction Neurobiol Aging 2014 35 2746 2760 10.1016/j.neurobiolaging.2014.06.004 25002035 · DOI · Paper page
  39. [54]Pelvig DP Pakkenberg H Stark AK Pakkenberg B Neocortical glial cell numbers in human brains Neurobiol Aging 2008 29 1754 1762 10.1016/J.NEUROBIOLAGING.2007.04.013 17544173 · DOI · Paper page
  40. [55]Pike CJ Cummings BJ Monzavi R Cotman CW P-amylotd-induced changes in cultured astrocytes parallel reactive astrocytosis associated with senile plaques in Alzheimer’s disease Neuroscience 1994 63 2 517 10.1016/0306-4522(94)90547-9 7891862 · DOI
  41. [57]Puvogel S Alsema A Kracht L Webster MJ Weickert CS Sommer IEC Eggen BJL Single-nucleus RNA sequencing of midbrain blood-brain barrier cells in schizophrenia reveals subtle transcriptional changes with overall preservation of cellular proportions and phenotypes Mol Psychiatry 2022 27 4731 4740 10.1038/s41380-022-01796-0 36192459 PMC9734060 · DOI
  42. [58]Quist E Trovato F Avaliani N Zetterdahl OG Gonzalez-Ramos A Hansen MG Kokaia M Canals I Ahlenius H Transcription factor-based direct conversion of human fibroblasts to functional astrocytes Stem Cell Rep 2022 17 1620 1635 10.1016/j.stemcr.2022.05.015 PMC9287681 35750047 · DOI
  43. [59]Radde R Bolmont T Kaeser SA Coomaraswamy J Lindau D Stoltze L Calhoun ME Jäggi F Wolburg H Gengler S Haass C Ghetti B Czech C Hölscher C Mathews PM Jucker M Aβ42-driven cerebral amyloidosis in transgenic mice reveals early and robust pathology EMBO Rep 2006 7 940 946 10.1038/sj.embor.7400784 16906128 PMC1559665 · DOI · Paper page
  44. [60]Scheel JR Ray J Gage FH Barlow C Quantitative analysis of gene expression in living adult neural stem cells by gene trapping Nat Methods 2005 2 363 369 10.1038/nmeth755 15846364 · DOI
  45. [61]Sharif A Duhem-Tonnelle V Allet C Baroncini M Loyens A Kerr-Conte J Collier F Blond S Ojeda SR Junier MP Prevot V Differential erbB signaling in astrocytes from the cerebral cortex and the hypothalamus of the human brain Glia 2009 57 362 379 10.1002/glia.20762 18803307 · DOI
  46. [62]Singh D Astrocytic and microglial cells as the modulators of neuroinflammation in Alzheimer’s disease J Neuroinflamm 2022 19 206 10.1186/s12974-022-02565-0 PMC9382837 35978311 · DOI · Paper page
  47. [63]Söllvander S Nikitidou E Brolin R Söderberg L Sehlin D Lannfelt L Erlandsson A Accumulation of amyloid-β by astrocytes result in enlarged endosomes and microvesicle-induced apoptosis of neurons Mol Neurodegener 2016 10.1186/s13024-016-0098-z 27176225 PMC4865996 · DOI · Paper page
  48. [65]Stogsdill JA Ramirez J Liu D Kim YH Baldwin KT Enustun E Ejikeme T Ji RR Eroglu C Astrocytic neuroligins control astrocyte morphogenesis and synaptogenesis Nature 2017 551 192 197 10.1038/nature24638 29120426 PMC5796651 · DOI · Paper page
  49. [66]Sutphen CL Jasielec MS Shah AR Macy EM Xiong C Vlassenko AG Benzinger TLS Stoops EEJ Vanderstichele HMJ Brix B Darby HD Vandijck MLJ Ladenson JH Morris JC Holtzman DM Fagan AM Longitudinal cerebrospinal fluid biomarker changes in preclinical Alzheimer disease during middle age JAMA Neurol 2015 72 1029 1042 10.1001/jamaneurol.2015.1285 26147946 PMC4570860 · DOI
  50. [67]Sweeney MD Sagare AP Zlokovic BV Blood-brain barrier breakdown in Alzheimer disease and other neurodegenerative disorders Nat Rev Neurol 2018 14 133 150 10.1038/nrneurol.2017.188 29377008 PMC5829048 · DOI · Paper page
  51. [69]Trotter JH, Dargaei Z, Sclip A, Essayan-Perez S, Liakath-Ali K, Raju K, Nabet A, Liu X, Wöhr M, Südhof TC (2020) Compartment-specific neurexin nanodomains orchestrate tripartite synapse assembly. 10.1101/2020.08.21.262097 · DOI
  52. [70]Verkhratsky A Nedergaard M Physiology of astroglia Physiol Rev 2018 98 239 389 10.1152/PHYSREV.00042.2016 29351512 PMC6050349 · DOI · Paper page
  53. [71]Virtanen P Gommers R Oliphant TE Haberland M Reddy T Cournapeau D Burovski E Peterson P Weckesser W Bright J van der Walt SJ Brett M Wilson J Millman KJ Mayorov N Nelson ARJ Jones E Kern R Larson E Carey CJ Polat İ Feng Y Moore EW VanderPlas J Laxalde D Perktold J Cimrman R Henriksen I Quintero EA Harris CR Archibald AM Ribeiro AH Pedregosa F van Mulbregt P Vijaykumar A Pietro BA Rothberg A Hilboll A Kloeckner A Scopatz A Lee A Rokem A Woods CN Fulton C Masson C Häggström C Fitzgerald C Nicholson DA Hagen DR Pasechnik DV Olivetti E Martin E Wieser E Silva F Lenders F Wilhelm F Young G Price GA Ingold GL Allen GE Lee GR Audren H Probst I Dietrich JP Silterra J Webber JT Slavič J Nothman J Buchner J Kulick J Schönberger JL de Miranda Cardoso JV Reimer J Harrington J Rodríguez JLC Nunez-Iglesias J Kuczynski J Tritz K Thoma M Newville M Kümmerer M Bolingbroke M Tartre M Pak M Smith NJ Nowaczyk N Shebanov N Pavlyk O Brodtkorb PA Lee P McGibbon RT Feldbauer R Lewis S Tygier S Sievert S Vigna S Peterson S More S Pudlik T Oshima T Pingel TJ Robitaille TP Spura T Jones TR Cera T Leslie T Zito T Krauss T Upadhyay U Halchenko YO Vázquez-Baeza Y SciPy 1.0: fundamental algorithms for scientific computing in Python Nat Methods 2020 17 261 272 10.1038/s41592-019-0686-2 32015543 PMC7056644 · DOI · Paper page
  54. [72]Vitvitsky VM Garg SK Keep RF Albin RL Banerjee R Na+ and K+ ion imbalances in Alzheimer’s disease Biochim Biophys Acta Mol Basis Dis 2012 1822 1671 1681 10.1016/j.bbadis.2012.07.004 PMC3444663 22820549 · DOI
  55. [73]Wang R Reddy PH Role of glutamate and NMDA receptors in Alzheimer’s disease J Alzheimer’s Dis 2017 57 1041 1048 10.3233/JAD-160763 27662322 PMC5791143 · DOI · Paper page
  56. [75]Wieduwilt MJ Moasser MM The epidermal growth factor receptor family: biology driving targeted therapeutics Cell Mol Life Sci 2008 65 1566 1584 10.1007/s00018-008-7440-8 18259690 PMC3060045 · DOI
  57. [77]Wolf FA Hamey FK Plass M Solana J Dahlin JS Göttgens B Rajewsky N Simon L Theis FJ PAGA: graph abstraction reconciles clustering with trajectory inference through a topology preserving map of single cells Genome Biol 2019 20 1 9 10.1186/s13059-019-1663-x 30890159 PMC6425583 · DOI · Paper page
  58. [78]Yeon GB Shin WH Yoo SH Kim D Jeon BM Park WU Bae Y Park JY You S Na D Kim DS NFIB induces functional astrocytes from human pluripotent stem cell-derived neural precursor cells mimicking in vivo astrogliogenesis J Cell Physiol 2021 236 7625 7641 10.1002/jcp.30405 33949692 · DOI
  59. [80]Zamanian JL Xu L Foo LC Nouri N Zhou L Giffard RG Barres BA Genomic analysis of reactive astrogliosis J Neurosci 2012 32 6391 6410 10.1523/JNEUROSCI.6221-11.2012 22553043 PMC3480225 · DOI · Paper page
  60. [81]Zecca L Youdim MBH Riederer P Connor JR Crichton RR Iron, brain ageing and neurodegenerative disorders Nat Rev Neurosci 2004 5 11 863 873 10.1038/NRN1537 15496864 · DOI · Paper page
  61. [82]Zenaro E Piacentino G Constantin G The blood–brain barrier in Alzheimer’s disease Neurobiol Dis 2017 107 41 56 10.1016/j.nbd.2016.07.007 27425887 PMC5600438 · DOI · Paper page
  62. [83]Zhang Y Sloan SA Clarke LE Caneda C Plaza CA Blumenthal PD Vogel H Steinberg GK Edwards MSB Li G Duncan JA Cheshier SH Shuer LM Chang EF Grant GA Gephart MGH Barres BA Purification and characterization of progenitor and mature human astrocytes reveals transcriptional and functional differences with mouse Neuron 2016 89 37 53 10.1016/j.neuron.2015.11.013 26687838 PMC4707064 · DOI · Paper page
  63. [84]Zhao H Cai Y Yang Z He D Shen B Acidosis leads to neurological disorders through overexciting cortical pyramidal neurons Biochem Biophys Res Commun 2011 415 224 228 10.1016/j.bbrc.2011.08.008 21856290 · DOI
  64. [85]Zhou Y Song WM Andhey PS Swain A Levy T Miller KR Poliani PL Cominelli M Grover S Gilfillan S Cella M Ulland TK Zaitsev K Miyashita A Ikeuchi T Sainouchi M Kakita A Bennett DA Schneider JA Nichols MR Beausoleil SA Ulrich JD Holtzman DM Artyomov MN Colonna M Human and mouse single-nucleus transcriptomics reveal TREM2-dependent and TREM2-independent cellular responses in Alzheimer’s disease Nat Med 2020 26 131 142 10.1038/s41591-019-0695-9 31932797 PMC6980793 · DOI · Paper page
  65. [86]Zhou Y Zhou B Pache L Chang M Khodabakhshi AH Tanaseichuk O Benner C Chanda SK Metascape provides a biologist-oriented resource for the analysis of systems-level datasets Nat Commun 2019 10.1038/s41467-019-09234-6 30944313 PMC6447622 · DOI · Paper page

Cited by

Sorted by citations

Authors
Dai, D. L., Li, M., & Lee, E. B.
Affiliations
University of Pennsylvania (US)
Corresponding author
Lee, Edward B.
ORCID
Venue
Acta Neuropathologica Communications
Publisher
Springer Science and Business Media LLC
Published
2023-08-02
Volume
11
Issue
1
Pages
127-127
ISSN
2051-5960 (ISSN-L)
DOI
10.1186/s40478-023-01624-8
PMC
PMC10398957
OpenAlex
W4385483291
Cited by
77
References
18
Citations by year
2026: 13 · 2025: 28 · 2024: 33 · 2023: 3
FWCI
14.74
Type
journal article
Language
en
Open access
Licence
Locations
  • Acta Neuropathologica Communications (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Funders
National Institute on Aging (P01AG066597, P30AG072979, U19AG062418, RF1AG065341, F30AG077858)
Topics
  • Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
  • Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Single-cell and spatial transcriptomics
Keywords
Alzheimer's disease, reactive astrocytes, astrocyte activation, astrocyte transcriptome, protoplasmic astrocyte, white matter astrocytes, ErbB4, NFIA, amyloid pathology, tau pathology, neuronal homeostasis, single-nucleus RNA sequencing, gene expression profiling, neuroinflammation, proteostasis
MeSH terms
Alzheimer Disease, Astrocytes, Brain, Humans, Gene Expression

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