Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Article
  • Published:

Effect of APOE alleles on the glial transcriptome in normal aging and Alzheimer’s disease

Nature Aging volume 1, pages 919–931 (2021)Cite this article

Subjects

Abstract

The roles of APOEε4 and APOEε2—the strongest genetic risk and protective factors for Alzheimer’s disease—in glial responses remain elusive. We tested the hypothesis that APOE alleles differentially impact glial responses by investigating their effects on the glial transcriptome from elderly control brains with no neuritic amyloid plaques. We identified a cluster of microglial genes that are upregulated in APOEε4 and downregulated in APOEε2 carriers relative to APOEε3 homozygotes. This microglia-APOE cluster is enriched in phagocytosis—including TREM2 and TYROBP—and proinflammatory genes, and is also detectable in brains with frequent neuritic plaques. Next, we tested these findings in APOE knock-in mice exposed to acute (lipopolysaccharide challenge) and chronic (cerebral β-amyloidosis) insults and found that these mice partially recapitulate human APOE-linked expression patterns. Thus, the APOEε4 allele might prime microglia towards a phagocytic and proinflammatory state through an APOE–TREM2–TYROBP axis in normal aging as well as in Alzheimer’s disease.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Fig. 1: Workflow of integrative analyses of APOE associations with microglia and astrocyte transcriptomic phenotypes.
Fig. 2: Identification of a microglial gene signature associated with APOE genotype in normal aging.
Fig. 3: The microglia-APOE signature is independent of known APOE effects on AD neuropathological changes.
Fig. 4: Astrocyte transcriptomic changes associated with APOE genotype in normal aging.
Fig. 5: Cross-validation of microglia-APOE cluster in APOE knock-in mice.

Similar content being viewed by others

Data availability

ROSMAP and MSBB RNA-seq data are available from the AMP-AD Knowledge Portal (https://doi.org/10.7303/syn3388564 and https://doi.org/10.7303/syn3157743, respectively). Mouse RNA-seq data from Zhao et. al. are available at the AMP-AD Knowledge Portal (https://doi.org/10.7303/syn20808171), and those from Nuriel et al. at Gene Expression Omnibus (no. GSE102334). The data from our APOE knock-in mice are available in Supplementary Table 4.

Code availability

Code for all data analyses is available on GitHub at https://mindds.github.io/apoe-glia.

References

  1. Kunkle, B. W. et al. Genetic meta-analysis of diagnosed Alzheimer’s disease identifies new risk loci and implicates Aβ, tau, immunity and lipid processing. Nat. Genet. 51, 414–430 (2019).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  2. Yamazaki, Y., Zhao, N., Caulfield, T. R., Liu, C.-C. & Bu, G. Apolipoprotein E and Alzheimer disease: pathobiology and targeting strategies. Nat. Rev. Neurol. 15, 501–518 (2019).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. Reiman, E. M. et al. Exceptionally low likelihood of Alzheimer’s dementia in APOE2 homozygotes from a 5,000-person neuropathological study. Nat. Commun. 11, 667 (2020).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. Serrano-Pozo, A., Qian, J., Monsell, S. E., Betensky, R. A. & Hyman, B. T. APOEε2 is associated with milder clinical and pathological Alzheimer disease. Ann. Neurol. 77, 917–929 (2015).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Ossenkoppele, R. et al. Prevalence of amyloid PET positivity in dementia syndromes: a meta-analysis. JAMA 313, 1939–1949 (2015).

    Article  PubMed Central  Google Scholar 

  6. Goldberg, T. E., Huey, E. D. & Devanand, D. P. Association of APOE e2 genotype with Alzheimer’s and non-Alzheimer’s neurodegenerative pathologies. Nat. Commun. 11, 4727 (2020).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. West, H. L., Rebeck, G. W. & Hyman, B. T. Frequency of the apolipoprotein E epsilon 2 allele is diminished in sporadic Alzheimer disease. Neurosci. Lett. 175, 46–48 (1994).

    Article  CAS  PubMed  Google Scholar 

  8. Serrano-Pozo, A., Das, S. & Hyman, B. T. APOE and Alzheimer’s disease: advances in genetics, pathophysiology, and therapeutic approaches. Lancet Neurol. 20, 68–80 (2021).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Serrano-Pozo, A. et al. Reactive glia not only associates with plaques but also parallels tangles in Alzheimer’s disease. Am. J. Pathol. 179, 1373–1384 (2011).

    Article  PubMed  PubMed Central  Google Scholar 

  10. Serrano-Pozo, A. et al. Differential relationships of reactive astrocytes and microglia to fibrillar amyloid deposits in Alzheimer disease. J. Neuropathol. Exp. Neurol. 72, 462–471 (2013).

    Article  CAS  PubMed  Google Scholar 

  11. Serrano-Pozo, A., Betensky, R. A., Frosch, M. P. & Hyman, B. T. Plaque-associated local toxicity increases over the clinical course of Alzheimer disease. Am. J. Pathol. 186, 375–384 (2016).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Lin, Y.-T. et al. APOE4 causes widespread molecular and cellular alterations associated with Alzheimer’s disease phenotypes in human iPSC-derived brain cell types. Neuron 98, 1141–1154 (2018).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Nuriel, T. et al. The endosomal–lysosomal pathway Is dysregulated by APOE4 expression in vivo. Front. Neurosci. 11, 702 (2017).

    Article  PubMed  PubMed Central  Google Scholar 

  14. Zhao, N. et al. Alzheimer’s risk factors age, APOE genotype, and sex drive distinct molecular pathways. Neuron 106, 727–742 (2020).

  15. Shi, Y. et al. ApoE4 markedly exacerbates tau-mediated neurodegeneration in a mouse model of tauopathy. Nature 549, 523–527 (2017).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  16. Shi, Y. et al. Microglia drive APOE-dependent neurodegeneration in a tauopathy mouse model. J. Exp. Med. 216, 2546–2561 (2019).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Fitz, N. F. et al. Trem2 deficiency differentially affects phenotype and transcriptome of human APOE3 and APOE4 mice. Mol. Neurodegener. 15, 41 (2020).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Konttinen, H. et al. PSEN1ΔE9, APPswe, and APOE4 confer disparate phenotypes in human iPSC-derived microglia. Stem Cell Rep. 13, 669–683 (2019).

    Article  CAS  Google Scholar 

  19. Julia, T. C. W. et al. Cholesterol and matrisome pathways dysregulated in human APOE ε4 glia. Preprint at bioRxiv https://doi.org/10.1101/713362 (2019).

  20. Olah, M. et al. A transcriptomic atlas of aged human microglia. Nat. Commun. 9, 539 (2018).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  21. Lefterov, I. et al. APOE2 orchestrated differences in transcriptomic and lipidomic profiles of postmortem AD brain. Alzheimers Res. Ther. 11, 113 (2019).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Conway, O. J. et al. ABI3 and PLCG2 missense variants as risk factors for neurodegenerative diseases in Caucasians and African Americans. Mol. Neurodegener. 13, 53 (2018).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Sims, R. et al. Rare coding variants in PLCG2, ABI3, and TREM2 implicate microglial-mediated innate immunity in Alzheimer’s disease. Nat. Genet. 49, 1373–1384 (2017).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Dalmasso, M. C. et al. Transethnic meta-analysis of rare coding variants in PLCG2, ABI3, and TREM2 supports their general contribution to Alzheimer’s disease. Transl. Psychiatry 9, 55 (2019).

    Article  PubMed  PubMed Central  Google Scholar 

  25. Haure-Mirande, J.-V. et al. Integrative approach to sporadic Alzheimer’s disease: deficiency of TYROBP in cerebral Aβ amyloidosis mouse normalizes clinical phenotype and complement subnetwork molecular pathology without reducing Aβ burden. Mol. Psychiatry 24, 431–446 (2019).

    Article  CAS  PubMed  Google Scholar 

  26. Zhang, B. et al. Integrated systems approach identifies genetic nodes and networks in late-onset Alzheimer’s disease. Cell 153, 707–720 (2013).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Han, S. H. et al. Apolipoprotein E is present in hippocampal neurons without neurofibrillary tangles in Alzheimer’s disease and in age-matched controls. Exp. Neurol. 128, 13–26 (1994).

    Article  CAS  PubMed  Google Scholar 

  28. Keren-Shaul, H. et al. A unique microglia type associated with restricting development of Alzheimer’s disease. Cell 169, 1276–1290 (2017).

    Article  CAS  PubMed  Google Scholar 

  29. Krasemann, S. et al. The TREM2-APOE pathway drives the transcriptional phenotype of dysfunctional microglia in neurodegenerative diseases. Immunity 47, 566–581 (2017).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. Zhou, Y. et al. Human and mouse single-nucleus transcriptomics reveal TREM2-dependent and TREM2-independent cellular responses in Alzheimer’s disease. Nat. Med. 26, 131–142 (2020).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. Srinivasan, K. et al. Untangling the brain’s neuroinflammatory and neurodegenerative transcriptional responses. Nat. Commun. 7, 11295 (2016).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. Kang, S. S. et al. Microglial translational profiling reveals a convergent APOE pathway from aging, amyloid, and tau. J. Exp. Med. 215, 2235–2245 (2018).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  33. Heneka, M. T. et al. Neuroinflammation in Alzheimer’s disease. Lancet Neurol. 14, 388–405 (2015).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  34. Perry, V. H. & Holmes, C. Microglial priming in neurodegenerative disease. Nat. Rev. Neurol. 10, 217–224 (2014).

    Article  CAS  PubMed  Google Scholar 

  35. Ismail, R. et al. The relationships between neuroinflammation, beta-amyloid and tau deposition in Alzheimer’s disease: a longitudinal PET study. J. Neuroinflammation 17, 151 (2020).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  36. Hashimoto, T. et al. Apolipoprotein E, especially apolipoprotein E4, increases the oligomerization of amyloid β peptide. J. Neurosci. 32, 15181–15192 (2012).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  37. Hori, Y., Hashimoto, T., Nomoto, H., Hyman, B. T. & Iwatsubo, T. Role of apolipoprotein E in Β-amyloidogenesis: isoform-specific effects on protofibril to fibril conversion of Aβ in vitro and brain Aβ deposition in vivo. J. Biol. Chem. 290, 15163–15174 (2015).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  38. Liu, C.-C. et al. ApoE4 accelerates early seeding of amyloid pathology. Neuron 96, 1024–1032 (2017).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  39. Hong, S. et al. Complement and microglia mediate early synapse loss in Alzheimer mouse models. Science 352, 712–716 (2016).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  40. Dejanovic, B. et al. Changes in the synaptic proteome in tauopathy and rescue of tau-induced synapse loss by C1q antibodies. Neuron 100, 1322–1336 (2018).

    Article  CAS  PubMed  Google Scholar 

  41. Wu, T. et al. Complement C3 is activated in human AD brain and is required for neurodegeneration in mouse models of amyloidosis and tauopathy. Cell Rep. 28, 2111–2123 (2019).

    Article  CAS  PubMed  Google Scholar 

  42. Shi, Q. et al. Complement C3 deficiency protects against neurodegeneration in aged plaque-rich APP/PS1 mice. Sci. Transl. Med. 9, eaaf6295 (2017).

    Article  PubMed  PubMed Central  Google Scholar 

  43. Serrano-Pozo, A., Frosch, M. P., Masliah, E. & Hyman, B. T. Neuropathological alterations in Alzheimer disease. Cold Spring Harb. Perspect. Med. 1, a006189 (2011).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  44. Stone, D. J., Molony, C., Suver, C., Schadt, E. E. & Potter, W. Z. ApoE genotyping as a progression-rate biomarker in phase II disease-modification trials for Alzheimer’s disease. Pharmacogenomics J. 10, 161–164 (2010).

    Article  CAS  PubMed  Google Scholar 

  45. Yu, L. et al. APOE ε4, Alzheimer’s disease pathology, cerebrovascular disease, and cognitive change over the years prior to death. Psychol. Aging 28, 1015–1023 (2013).

    Article  PubMed  Google Scholar 

  46. Qian, J., Betensky, R. A., Hyman, B. T. & Serrano-Pozo, A. Association of APOE genotype with heterogeneity of cognitive decline rate in Alzheimer disease. Neurology 96, e2414–e2428 (2021).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  47. Guerreiro, R. et al. TREM2 variants in Alzheimer’s disease. N. Engl. J. Med. 368, 117–127 (2013).

    Article  CAS  PubMed  Google Scholar 

  48. Jonsson, T. et al. Variant of TREM2 associated with the risk of Alzheimer’s disease. N. Engl. J. Med. 368, 107–116 (2013).

    Article  CAS  PubMed  Google Scholar 

  49. Wang, Y. et al. TREM2-mediated early microglial response limits diffusion and toxicity of amyloid plaques. J. Exp. Med. 213, 667–675 (2016).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  50. Parhizkar, S. et al. Loss of TREM2 function increases amyloid seeding but reduces plaque-associated ApoE. Nat. Neurosci. 22, 191–204 (2019).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  51. Leyns, C. E. G. et al. TREM2 function impedes tau seeding in neuritic plaques. Nat. Neurosci. 22, 1217–1222 (2019).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  52. Bemiller, S. M. et al. TREM2 deficiency exacerbates tau pathology through dysregulated kinase signaling in a mouse model of tauopathy. Mol. Neurodegener. 12, 74 (2017).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  53. Leyns, C. E. G. et al. TREM2 deficiency attenuates neuroinflammation and protects against neurodegeneration in a mouse model of tauopathy. Proc. Natl Acad. Sci. USA 114, 11524–11529 (2017).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  54. Gratuze, M. et al. Impact of TREM2R47H variant on tau pathology-induced gliosis and neurodegeneration. J. Clin. Invest. 130, 4954–4968 (2020).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  55. Ulrich, J. D. et al. ApoE facilitates the microglial response to amyloid plaque pathology. J. Exp. Med. 215, 1047–1058 (2018).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  56. Serrano-Pozo, A. et al. Stable size distribution of amyloid plaques over the course of Alzheimer disease. J. Neuropathol. Exp. Neurol. 71, 694–701 (2012).

    Article  PubMed  Google Scholar 

  57. Haure-Mirande, J.-V. et al. Deficiency of TYROBP, an adapter protein for TREM2 and CR3 receptors, is neuroprotective in a mouse model of early Alzheimer’s pathology. Acta Neuropathol. 134, 769–788 (2017).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  58. Audrain, M. et al. Integrative approach to sporadic Alzheimer’s disease: deficiency of TYROBP in a tauopathy mouse model reduces C1q and normalizes clinical phenotype while increasing spread and state of phosphorylation of tau. Mol. Psychiatry 24, 1383–1397 (2019).

    Article  CAS  PubMed  Google Scholar 

  59. Audrain, M. et al. Reactive or transgenic increase in microglial TYROBP reveals a TREM2-independent TYROBP–APOE link in wild-type and Alzheimer’s-related mice. Alzheimers Dement. 17, 149–163 (2021).

  60. Zhu, Y. et al. APOE genotype alters glial activation and loss of synaptic markers in mice. Glia 60, 559–569 (2012).

    Article  PubMed  PubMed Central  Google Scholar 

  61. Rodriguez, G. A., Tai, L. M., LaDu, M. J. & Rebeck, G. W. Human APOE4 increases microglia reactivity at Aβ plaques in a mouse model of Aβ deposition. J. Neuroinflammation 11, 111 (2014).

    Article  PubMed  PubMed Central  Google Scholar 

  62. Ising, C. et al. NLRP3 inflammasome activation drives tau pathology. Nature 575, 669–673 (2019).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  63. Masuda, T. et al. IRF8 is a critical transcription factor for transforming microglia into a reactive phenotype. Cell Rep. 1, 334–340 (2012).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  64. Grubman, A. et al. A single-cell atlas of entorhinal cortex from individuals with Alzheimer’s disease reveals cell-type-specific gene expression regulation. Nat. Neurosci. 22, 2087–2097 (2019).

    Article  CAS  PubMed  Google Scholar 

  65. Mathys, H. et al. Single-cell transcriptomic analysis of Alzheimer’s disease. Nature 570, 332–337 (2019).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  66. Wan, Y.-W. et al. Meta-analysis of the Alzheimer’s disease human brain transcriptome and functional dissection in mouse models. Cell Rep. 32, 107908 (2020).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  67. Gosselin, D. et al. An environment-dependent transcriptional network specifies human microglia identity. Science 356, eaal3222 (2017).

  68. Friedman, B. A. et al. Diverse brain myeloid expression profiles reveal distinct microglial activation states and aspects of Alzheimer’s disease not evident in mouse models. Cell Rep. 22, 832–847 (2018).

    Article  CAS  PubMed  Google Scholar 

  69. Gearing, M., Rebeck, G. W., Hyman, B. T., Tigges, J. & Mirra, S. S. Neuropathology and apolipoprotein E profile of aged chimpanzees: implications for Alzheimer disease. Proc. Natl Acad. Sci. USA 91, 9382–9386 (1994).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  70. Patrick, E. et al. Deconvolving the contributions of cell-type heterogeneity on cortical gene expression. PLoS Comput. Biol. 16, e1008120 (2020).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  71. Wang, X. et al. Deciphering cellular transcriptional alterations in Alzheimer’s disease brains. Mol. Neurodegener. 15, 38 (2020).

    Article  PubMed  PubMed Central  Google Scholar 

  72. Zhang, Y. et al. Purification and characterization of progenitor and mature human astrocytes reveals transcriptional and functional differences with mouse. Neuron 89, 37–53 (2016).

    Article  CAS  PubMed  Google Scholar 

  73. De Jager, P. L. et al. A multi-omic atlas of the human frontal cortex for aging and Alzheimer’s disease research. Sci. Data 5, 180142 (2018).

    Article  PubMed  PubMed Central  Google Scholar 

  74. Wang, M. et al. The Mount Sinai cohort of large-scale genomic, transcriptomic and proteomic data in Alzheimer’s disease. Sci. Data 5, 180185 (2018).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  75. Mirra, S. S. et al. The Consortium to Establish a Registry for Alzheimer’s Disease (CERAD). Part II. Standardization of the neuropathologic assessment of Alzheimer’s disease. Neurology 41, 479–486 (1991).

    Article  CAS  PubMed  Google Scholar 

  76. Braak, H. & Braak, E. Neuropathological stageing of Alzheimer-related changes. Acta Neuropathol. 82, 239–259 (1991).

    Article  CAS  PubMed  Google Scholar 

  77. Wang, B. et al. Similarity network fusion for aggregating data types on a genomic scale. Nat. Methods 11, 333–337 (2014).

    Article  CAS  PubMed  Google Scholar 

  78. Ritchie, M. E. et al. limma Powers differential expression analyses for RNA-sequencing and microarray studies. Nucleic Acids Res. 43, e47 (2015).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  79. Benjamini, Y. & Hochberg, Y. Controlling the false discovery rate: a practical and powerful approach to multiple testing. J. R. Stat. Soc. Series B Stat. Methodol. 57, 289–300 (1995).

    Google Scholar 

  80. Huynh, T.-P. V. et al. Lack of hepatic apoE does not influence early Aβ deposition: observations from a new APOE knock-in model. Mol. Neurodegener. 14, 37 (2019).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  81. Jankowsky, J. L. et al. Mutant presenilins specifically elevate the levels of the 42 residue beta-amyloid peptide in vivo: evidence for augmentation of a 42-specific gamma secretase. Hum. Mol. Genet. 13, 159–170 (2004).

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgements

The results published here are in whole or in part based on data obtained from the AD Knowledge Portal (https://adknowledgeportal.org). ROSMAP data were provided by the Rush Alzheimer’s Disease Center, Rush University Medical Center, Chicago, IL, USA. Data collection was supported through funding by NIA grant nos. P30AG10161 (ROS), R01AG15819 (ROSMAP; genomics and RNA-seq), R01AG17917 (MAP), R01AG30146, R01AG36042 (5hC methylation, ATAC–seq), RC2AG036547 (H3K9Ac), R01AG36836 (RNA-seq), R01AG48015 (monocyte RNA-seq), RF1AG57473 (single-nucleus RNA-seq), U01AG32984 (genomic and whole-exome sequencing), U01AG46152 (ROSMAP AMP-AD, targeted proteomics), U01AG46161(TMT proteomics), U01AG61356 (whole-genome sequencing, targeted proteomics, ROSMAP AMP-AD), the Illinois Department of Public Health (ROSMAP) and the Translational Genomics Research Institute (genomic). Additional phenotypic data can be requested at www.radc.rush.edu. MSBB data were generated from postmortem brain tissue collected through the Mount Sinai VA Medical Center Brain Bank and were provided by E. Schadt from Mount Sinai School of Medicine. This work was supported by the National Institute on Aging (nos. K08AG064039 to A.S.-P., T32AG000222-27 to R.J.J. and P30AG062421 to S.D. and B.T.H.), the Alzheimer’s Association (nos. AACF-17-524184 and AACF-17-524184-RAPID to A.S.-P.), the JPB Foundation (to B.T.H.) and the Jack Satter Foundation (to A.S.-P. and S.D.).

Author information

Authors and Affiliations

  1. Department of Neurology, Massachusetts General Hospital, Boston, MA, USA

    Alberto Serrano-Pozo, Zhaozhi Li, Ayush Noori, Huong N. Nguyen, Aziz Mezlini, Liang Li, Eloise Hudry, Rosemary J. Jackson, Bradley T. Hyman & Sudeshna Das

  2. Massachusetts Alzheimer’s Disease Research Center, Charlestown, MA, USA

    Alberto Serrano-Pozo, Zhaozhi Li, Ayush Noori, Aziz Mezlini, Bradley T. Hyman & Sudeshna Das

  3. Harvard Medical School, Boston, MA, USA

    Alberto Serrano-Pozo, Aziz Mezlini, Eloise Hudry, Rosemary J. Jackson, Bradley T. Hyman & Sudeshna Das

Authors
  1. Alberto Serrano-Pozo
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Zhaozhi Li
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Ayush Noori
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Huong N. Nguyen
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Aziz Mezlini
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Liang Li
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Eloise Hudry
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Rosemary J. Jackson
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Bradley T. Hyman
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Sudeshna Das
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

A.S.-P. conducted conceptualization, supervision, writing of the original draft, writing, review and editing and funding acquisition. Z.L. was responsible for formal analysis, software, visualization, data curation, writing, review and editing. A.N. undertook formal analysis, software, visualization, data curation, writing, review and editing. H.N.N., A.M. and L.L. conducted investigations. E.H. contributed to conceptualization. R.J.J. undertook formal analysis, supervision, writing, review and editing. B.T.H. contributed to conceptualization, resources, writing, review, editing and funding acquisition. S.D. was involved in conceptualization, methodology, supervision, resources, project administration, writing of the original draft, writing, review, editing and funding acquisition.

Corresponding author

Correspondence to Sudeshna Das.

Ethics declarations

Competing interests

The authors declare no competing interests.

Additional information

Peer review information Nature Aging thanks the anonymous reviewers for their contribution to the peer review of this work.

Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Supplementary information

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Serrano-Pozo, A., Li, Z., Noori, A. et al. Effect of APOE alleles on the glial transcriptome in normal aging and Alzheimer’s disease. Nat Aging 1, 919–931 (2021). https://doi.org/10.1038/s43587-021-00123-6

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/s43587-021-00123-6

This article is cited by

Search

Advanced search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing