CoChat
Sign Up
Cited by 69Alzheimer's disease research and treatmentsNeuroinflammation and Neurodegeneration MechanismsDementia and Cognitive Impairment Research

Systematic review of human post‐mortem immunohistochemical studies and bioinformatics analyses unveil the complexity of astrocyte reaction in Alzheimer's disease

Open access
Viejo, Lucía, Noori, Ayush, Merrill, Emily, Das, Sudeshna, Hyman, Bradley T., Serrano‐Pozo, Alberto·2022·Neuropathology and Applied Neurobiology
DOI 10.1111/nan.12753PMC PMC8766893
Open this paper in CoChat — free accountOpen PDF

Abstract

Aims: Reactive astrocytes in Alzheimer's disease (AD) have traditionally been demonstrated by increased glial fibrillary acidic protein (GFAP) immunoreactivity; however, astrocyte reaction is a complex and heterogeneous phenomenon involving multiple astrocyte functions beyond cytoskeletal remodelling. To better understand astrocyte reaction in AD, we conducted a systematic review of astrocyte immunohistochemical studies in post‐mortem AD brains followed by bioinformatics analyses on the extracted reactive astrocyte markers. Methods: NCBI PubMed, APA PsycInfo and WoS‐SCIE databases were interrogated for original English research articles with the search terms ‘Alzheimer's disease’ AND ‘astrocytes.’ Bioinformatics analyses included protein–protein interaction network analysis, pathway enrichment, and transcription factor enrichment, as well as comparison with public human ‐omics datasets. Results: A total of 306 articles meeting eligibility criteria rendered 196 proteins, most of which were reported to be upregulated in AD vs control brains. Besides cytoskeletal remodelling (e.g., GFAP), bioinformatics analyses revealed a wide range of functional alterations including neuroinflammation (e.g., IL6, MAPK1/3/8 and TNF), oxidative stress and antioxidant defence (e.g., MT1A/2A, NFE2L2, NOS1/2/3, PRDX6 and SOD1/2), lipid metabolism (e.g., APOE, CLU and LRP1), proteostasis (e.g., cathepsins, CRYAB and HSPB1/2/6/8), extracellular matrix organisation (e.g., CD44, MMP1/3 and SERPINA3), and neurotransmission (e.g., CHRNA7, GABA, GLUL, GRM5, MAOB and SLC1A2), among others. CTCF and ESR1 emerged as potential transcription factors driving these changes. Comparison with published ‐omics datasets validated our results, demonstrating a significant overlap with reported transcriptomic and proteomic changes in AD brains and/or CSF. Conclusions: Our systematic review of the neuropathological literature reveals the complexity of AD reactive astrogliosis. We have shared these findings as an online resource available at www.astrocyteatlas.org.

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Integrity signals

Registry

Crossref · 10.1111/nan.12753

Cites

24 of 24 references verified0 citation errors · 0 not checkable

Statistics

Claims the paper makes

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

  • Many upregulated gene products in reactive astrocytes have been demonstrated in AD reactive astrocytes via immunohistochemistry, especially near dense-core, typically neuritic, Aβ plaques.

    “many of these upregulated gene products have been demonstrated in AD reactive astrocytes via immunohistochemistry, especially near dense-core, typically neuritic, Aβ plaques53”

    From Astrocyte transcriptomic changes along the spatiotemporal progression of Alzheimer’s disease (2024) · cites this paper as [53]

    The Results (Functional characterisation of markers of astrocyte reaction; page unavailable) review immunohistochemical evidence that many proteins are increased in AD reactive astrocytes. The claim’s plaque qualifier is not supported as stated: the review describes Aβ-immunoreactive astrocytes especially near diffuse Aβ deposits, not especially near dense-core, typically neuritic plaques. (LLM, conf=0.87)

    Experimental — accuracy not yet measured

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

The self-check needs the paper’s full text.

Cites

Flagged first, then by citations

Research works printed but not linked: 270

  1. [2]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 Neuroinflammation. 2020; 17(1): 227. 32736565 PMC7393869
  2. [3]Perez‐Nievas BG, Serrano‐Pozo A. Deciphering the astrocyte reaction in Alzheimer's disease. Front Aging Neurosci. 2018; 10: 114. 29922147 PMC5996928
  3. [5]Ferrer I. Diversity of astroglial responses across human neurodegenerative disorders and brain aging. Brain Pathol Zurich Switz. 2017; 27(5): 645‐ 674. PMC8029391 28804999
  4. [6]Verkerke M, Hol EM, Middeldorp J. Physiological and pathological ageing of astrocytes in the human brain. Neurochem Res. 2021 Feb 8. PMC8437874 33559106
  5. [7]Bayraktar OA, Bartels T, Holmqvist S, et al. Astrocyte layers in the mammalian cerebral cortex revealed by a single‐cell in situ transcriptomic map. Nat Neurosci. 2020; 23(4): 500‐ 509. 32203496 PMC7116562
  6. [10]Serrano‐Pozo A, Betensky RA, Frosch MP, Hyman BT. Plaque‐associated local toxicity increases over the clinical course of Alzheimer disease. Am J Pathol. 2016; 186(2): 375‐ 384. 26687817 PMC4729270
  7. [11]Prokop S, Miller KR, Labra SR, et al. Impact of TREM2 risk variants on brain region‐specific immune activation and plaque microenvironment in Alzheimer's disease patient brain samples. Acta Neuropathol (Berl). 2019; 138(4): 613‐ 630. 31350575 PMC6939638
  8. [13]Liberati A, Altman DG, Tetzlaff J, et al. The PRISMA statement for reporting systematic reviews and meta‐analyses of studies that evaluate health care interventions: explanation and elaboration. PLoS Med. 2009; 6(7): e1000100. 19621070 PMC2707010
  9. [14]The UniProt Consortium. UniProt: the universal protein knowledgebase in 2021. Nucleic Acids Res. 2021 Jan 8; 49(D1): D480‐ D409. 33237286 PMC7778908
  10. [15]Tweedie S, Braschi B, Gray K, et al. Genenames.org: the HGNC and VGNC resources in 2021. Nucleic Acids Res. 2021; 49(D1): D939‐ D946. 33152070 PMC7779007
  11. [16]Ashburner M, Ball CA, Blake JA, et al. Gene Ontology: tool for the unification of biology. Nat Genet. 2000; 25(1): 25‐ 29. 10802651 PMC3037419
  12. [17]Jassal B, Matthews L, Viteri G, et al. The Reactome pathway knowledgebase. Nucleic Acids Res. 2020; 48(D1): D498‐ D503. 31691815 PMC7145712
  13. [18]Liberzon A, Subramanian A, Pinchback R, Thorvaldsdóttir H, Tamayo P, Mesirov JP. Molecular signatures database (MSigDB) 3.0. Bioinformatics. 2011 Jun 15; 27(12): 1739‐ 1740. 21546393 PMC3106198
  14. [19]The Gene Ontology Consortium. The gene ontology resource: 20 years and still GOing strong. Nucleic Acids Res. 2019; 47: D330‐ D338. 30395331 PMC6323945
  15. [20]Szklarczyk D, Gable AL, Lyon D, et al. STRING v11: protein‐protein association networks with increased coverage, supporting functional discovery in genome‐wide experimental datasets. Nucleic Acids Res. 2019; 47(D1): D607‐ D613. 30476243 PMC6323986
  16. [21]Puente‐Santamaria L, Wasserman WW, del Peso L. TFEA.ChIP: a tool kit for transcription factor binding site enrichment analysis capitalizing on ChIP‐seq datasets. Bioinforma Oxf Engl. 2019; 35(24): 5339‐ 5340. 31347689
  17. [22]Kuleshov MV, Jones MR, Rouillard AD, et al. Enrichr: a comprehensive gene set enrichment analysis web server 2016 update. Nucleic Acids Res. 2016; 44(W1): W90‐ W97. 27141961 PMC4987924
  18. [23]Chèneby J, Gheorghe M, Artufel M, Mathelier A, Ballester B. ReMap 2018: an updated atlas of regulatory regions from an integrative analysis of DNA‐binding ChIP‐seq experiments. Nucleic Acids Res. 2018; 46(D1): D267‐ D275. 29126285 PMC5753247
  19. [24]Fishilevich S, Nudel R, Rappaport N, et al. GeneHancer: genome‐wide integration of enhancers and target genes in GeneCards. Database [Internet]. 2017 Jan 1 [cited 2021 Feb 28];2017(bax028). Available from: 10.1093/database/bax028 PMC5467550 28605766 · DOI
  20. [25]Dunham I, Kundaje A, Aldred SF, et al. An integrated encyclopedia of DNA elements in the human genome. Nature. 2012; 489(7414): 57‐ 74. 22955616 PMC3439153
  21. [26]Lachmann A, Xu H, Krishnan J, Berger SI, Mazloom AR, Ma'ayan A. ChEA: transcription factor regulation inferred from integrating genome‐wide ChIP‐X experiments. Bioinforma Oxf Engl. 2010; 26(19): 2438‐ 2444. PMC2944209 20709693
  22. [27]Simpson JE, Ince PG, Shaw PJ, et al. Microarray analysis of the astrocyte transcriptome in the aging brain: relationship to Alzheimer's pathology and APOE genotype. Neurobiol Aging. 2011; 32(10): 1795‐ 1807. 21705112
  23. [29]Johnson ECB, Dammer EB, Duong DM, et al. Large‐scale proteomic analysis of Alzheimer's disease brain and cerebrospinal fluid reveals early changes in energy metabolism associated with microglia and astrocyte activation. Nat Med. 2020; 26(5): 769‐ 780. 32284590 PMC7405761
  24. [30]Middeldorp J, van den Berge SA, Aronica E, Speijer D, Hol EM. Specific human astrocyte subtype revealed by affinity purified GFAP antibody; unpurified serum cross‐reacts with neurofilament‐L in Alzheimer. PloS One. 2009; 4(11): e7663. 19888461 PMC2766629
  25. [31]Kamphuis W, Middeldorp J, Kooijman L, et al. Glial fibrillary acidic protein isoform expression in plaque related astrogliosis in Alzheimer's disease. Neurobiol Aging. 2014; 35(3): 492‐ 510. 24269023
  26. [32]Mouser PE, Head E, Ha K‐H, Rohn TT. Caspase‐mediated cleavage of glial fibrillary acidic protein within degenerating astrocytes of the Alzheimer's disease brain. Am J Pathol. 2006; 168(3): 936‐ 946. 16507909 PMC1606516
  27. [33]Colombo JA, Quinn B, Puissant V. Disruption of astroglial interlaminar processes in Alzheimer's disease. Brain Res Bull. 2002; 58(2): 235‐ 242. 12127023
  28. [34]Pugliese M, Rodríguez MJ, Gimeno‐Bayon J, et al. Alzheimer's disease modifies progenitor cell expression of monoamine oxidase B in the subventricular zone. J Neurosci Res. 2010; 88(12): 2588‐ 2597. 20648649
  29. [35]Zhang W, Han SW, McKeel DW, Goate A, Wu JY. Interaction of presenilins with the filamin family of actin‐binding proteins. J Neurosci off J Soc Neurosci. 1998; 18(3): 914‐ 922. PMC2042137 9437013
  30. [36]Bosman GJ, Renkawek K, van Workum FP, Bartholomeus IG, de Grip WJ. Involvement of neuronal anion exchange proteins in cell death in Alzheimer's disease. Gerontology. 1997; 43(1–2): 67‐ 78. 8996830
  31. [37]Bouvier DS, Jones EV, Quesseveur G, et al. High resolution dissection of reactive glial nets in Alzheimer's disease. Sci Rep. 2016; 6: 24544. 27090093 PMC4835751
  32. [38]Griffin WS, Stanley LC, Ling C, et al. Brain interleukin 1 and S‐100 immunoreactivity are elevated in Down syndrome and Alzheimer disease. Proc Natl Acad Sci U S a. 1989; 86(19): 7611‐ 7615. 2529544 PMC298116
  33. [39]Thal DR, Schober R, Birkenmeier G. The subunits of alpha2‐macroglobulin receptor/low density lipoprotein receptor‐related protein, native and transformed alpha2‐macroglobulin and interleukin 6 in Alzheimer's disease. Brain Res. 1997; 777(1–2): 223‐ 227. 9449432
  34. [40]Sokolova A, Hill MD, Rahimi F, Warden LA, Halliday GM, Shepherd CE. Monocyte chemoattractant protein‐1 plays a dominant role in the chronic inflammation observed in Alzheimer's disease. Brain Pathol Zurich Switz. 2009; 19(3): 392‐ 398. PMC8094842 18637012
  35. [41]Ojala J, Alafuzoff I, Herukka S‐K, van Groen T, Tanila H, Pirttilä T. Expression of interleukin‐18 is increased in the brains of Alzheimer's disease patients. Neurobiol Aging. 2009; 30(2): 198‐ 209. 17658666
  36. [42]Xiong Z, Thangavel R, Kempuraj D, Yang E, Zaheer S, Zaheer A. Alzheimer's disease: evidence for the expression of interleukin‐33 and its receptor ST2 in the brain. J Alzheimers Dis JAD. 2014; 40(2): 297‐ 308. 24413615 PMC4015800
  37. [43]Katsuse O, Iseki E, Kosaka K. Immunohistochemical study of the expression of cytokines and nitric oxide synthases in brains of patients with dementia with Lewy bodies. Neuropathol off J Jpn Soc Neuropathol. 2003; 23(1): 9‐ 15. 12722921
  38. [44]Xia MQ, Qin SX, Wu LJ, Mackay CR, Hyman BT. Immunohistochemical study of the beta‐chemokine receptors CCR3 and CCR5 and their ligands in normal and Alzheimer's disease brains. Am J Pathol. 1998; 153(1): 31‐ 37. 9665462 PMC1852933
  39. [46]Rostasy K, Egles C, Chauhan A, et al. SDF‐1alpha is expressed in astrocytes and neurons in the AIDS dementia complex: an in vivo and in vitro study. J Neuropathol Exp Neurol. 2003; 62(6): 617‐ 626. 12834106
  40. [48]Yermakova AV, O'Banion MK. Downregulation of neuronal cyclooxygenase‐2 expression in end stage Alzheimer's disease. Neurobiol Aging. 2001; 22(6): 823‐ 836. 11754989
  41. [49]Stephenson DT, Lemere CA, Selkoe DJ, Clemens JA. Cytosolic phospholipase A2 (cPLA2) immunoreactivity is elevated in Alzheimer's disease brain. Neurobiol Dis. 1996; 3(1): 51‐ 63. 9173912
  42. [50]Mohri I, Kadoyama K, Kanekiyo T, et al. Hematopoietic prostaglandin D synthase and DP1 receptor are selectively upregulated in microglia and astrocytes within senile plaques from human patients and in a mouse model of Alzheimer disease. J Neuropathol Exp Neurol. 2007; 66(6): 469‐ 480. 17549007
  43. [51]Chaudhry UA, Zhuang H, Crain BJ, Doré S. Elevated microsomal prostaglandin‐E synthase‐1 in Alzheimer's disease. Alzheimers Dement J Alzheimers Assoc. 2008; 4(1): 6‐ 13. PMC2500207 18631945
  44. [52]de Wit NM, Snkhchyan H, den Hoedt S, et al. Altered sphingolipid balance in capillary cerebral amyloid angiopathy. J Alzheimers Dis JAD. 2017; 60(3): 795‐ 807. 27662305
  45. [53]Brana C, Frossard MJ, Pescini Gobert R, Martinier N, Boschert U, Seabrook TJ. Immunohistochemical detection of sphingosine‐1‐phosphate receptor 1 and 5 in human multiple sclerosis lesions. Neuropathol Appl Neurobiol. 2014; 40(5): 564‐ 578. 23551178
  46. [54]Abdul HM, Sama MA, Furman JL, et al. Cognitive decline in Alzheimer's disease is associated with selective changes in calcineurin/NFAT signaling. J Neurosci off J Soc Neurosci. 2009; 29(41): 12957‐ 12969. PMC2782445 19828810
  47. [55]Terai K, Matsuo A, McGeer PL. Enhancement of immunoreactivity for NF‐kappa B in the hippocampal formation and cerebral cortex of Alzheimer's disease. Brain Res. 1996; 735(1): 159‐ 168. 8905182
  48. [57]Shijo M, Honda H, Suzuki SO, et al. Association of adipocyte enhancer‐binding protein 1 with Alzheimer's disease pathology in human hippocampi. Brain Pathol Zurich Switz. 2018; 28(1): 58‐ 71. PMC8028652 27997051
  49. [58]Li R, Strohmeyer R, Liang Z, Lue L‐F, Rogers J. CCAAT/enhancer binding protein delta (C/EBPdelta) expression and elevation in Alzheimer's disease. Neurobiol Aging. 2004; 25(8): 991‐ 999. 15212823
  50. [59]Thangavel R, Stolmeier D, Yang X, Anantharam P, Zaheer A. Expression of glia maturation factor in neuropathological lesions of Alzheimer's disease. Neuropathol Appl Neurobiol. 2012; 38(6): 572‐ 581. 22035352 PMC3290752
  51. [60]Stolmeier D, Thangavel R, Anantharam P, Khan MM, Kempuraj D, Zaheer A. Glia maturation factor expression in hippocampus of human Alzheimer's disease. Neurochem Res. 2013; 38(8): 1580‐ 1589. 23640177 PMC3692596
  52. [61]Craig‐Schapiro R, Perrin RJ, Roe CM, et al. YKL‐40: a novel prognostic fluid biomarker for preclinical Alzheimer's disease. Biol Psychiatry. 2010; 68(10): 903‐ 912. 21035623 PMC3011944
  53. [62]Querol‐Vilaseca M, Colom‐Cadena M, Pegueroles J, et al. YKL‐40 (Chitinase 3‐like I) is expressed in a subset of astrocytes in Alzheimer's disease and other tauopathies. J Neuroinflammation. 2017; 14(1): 118. 28599675 PMC5466718
  54. [63]Llorens F, Thüne K, Tahir W, et al. YKL‐40 in the brain and cerebrospinal fluid of neurodegenerative dementias. Mol Neurodegener. 2017; 12(1): 83. 29126445 PMC5681777
  55. [64]Moreno‐Rodriguez M, Perez SE, Nadeem M, Malek‐Ahmadi M, Mufson EJ. Frontal cortex chitinase and pentraxin neuroinflammatory alterations during the progression of Alzheimer's disease. J Neuroinflammation. 2020; 17(1): 58. 32066474 PMC7025403
  56. [66]Gui Y, Marks JD, Das S, Hyman BT, Serrano‐Pozo A. Characterization of the 18 kDa translocator protein (TSPO) expression in post‐mortem normal and Alzheimer's disease brains. Brain Pathol Zurich Switz. 2020; 30(1): 151‐ 164. PMC6904423 31276244
  57. [67]Takeda A, Yasuda T, Miyata T, et al. Advanced glycation end products co‐localized with astrocytes and microglial cells in Alzheimer's disease brain. Acta Neuropathol (Berl). 1998; 95(6): 555‐ 558. 9650745
  58. [68]Takeda A, Wakai M, Niwa H, et al. Neuronal and glial advanced glycation end product [Nepsilon‐(carboxymethyl)lysine] in Alzheimer's disease brains. Acta Neuropathol (Berl). 2001; 101(1): 27‐ 35. 11194938
  59. [70]Wang MY, Ross‐Cisneros FN, Aggarwal D, Liang C‐Y, Sadun AA. Receptor for advanced glycation end products is upregulated in optic neuropathy of Alzheimer's disease. Acta Neuropathol (Berl). 2009; 118(3): 381‐ 389. 19277685 PMC2867613
  60. [71]Myung N‐H, Zhu X, Kruman II, et al. Evidence of DNA damage in Alzheimer disease: phosphorylation of histone H2AX in astrocytes. Age Dordr Neth. 2008 Dec; 30(4): 209‐ 215. PMC2585649 19424844
  61. [72]Simpson JE, Ince PG, Haynes LJ, et al. Population variation in oxidative stress and astrocyte DNA damage in relation to Alzheimer‐type pathology in the ageing brain. Neuropathol Appl Neurobiol. 2010; 36(1): 25‐ 40. 19422529
  62. [73]Waller R, Murphy M, Garwood CJ, et al. Metallothionein‐I/II expression associates with the astrocyte DNA damage response and not Alzheimer‐type pathology in the aging brain. Glia. 2018; 66(11): 2316‐ 2323. 30098078
  63. [74]Kawaguchi‐Niida M, Shibata N, Morikawa S, et al. Crotonaldehyde accumulates in glial cells of Alzheimer's disease brain. Acta Neuropathol (Berl). 2006; 111(5): 422‐ 429. 16538519
  64. [75]Maki RA, Tyurin VA, Lyon RC, et al. Aberrant expression of myeloperoxidase in astrocytes promotes phospholipid oxidation and memory deficits in a mouse model of Alzheimer disease. J Biol Chem. 2009; 284(5): 3158‐ 3169. 19059911 PMC2631957
  65. [76]Simic G, Lucassen PJ, Krsnik Z, et al. nNOS expression in reactive astrocytes correlates with increased cell death related DNA damage in the hippocampus and entorhinal cortex in Alzheimer's disease. Exp Neurol. 2000; 165(1): 12‐ 26. 10964481
  66. [77]Wallace MN, Geddes JG, Farquhar DA, Masson MR. Nitric oxide synthase in reactive astrocytes adjacent to beta‐amyloid plaques. Exp Neurol. 1997; 144(2): 266‐ 272. 9168828
  67. [78]de la Monte SM, Bloch KD. Aberrant expression of the constitutive endothelial nitric oxide synthase gene in Alzheimer disease. Mol Chem Neuropathol. 1997; 30(1–2): 139‐ 159. 9138425
  68. [79]Ramsey CP, Glass CA, Montgomery MB, et al. Expression of Nrf2 in neurodegenerative diseases. J Neuropathol Exp Neurol. 2007; 66(1): 75‐ 85. 17204939 PMC2253896
  69. [80]Raha AA, Vaishnav RA, Friedland RP, Bomford A, Raha‐Chowdhury R. The systemic iron‐regulatory proteins hepcidin and ferroportin are reduced in the brain in Alzheimer's disease. Acta Neuropathol Commun. 2013; 1: 55. 24252754 PMC3893417
  70. [81]Zambenedetti P, Giordano R, Zatta P. Metallothioneins are highly expressed in astrocytes and microcapillaries in Alzheimer's disease. J Chem Neuroanat. 1998; 15(1): 21‐ 26. 9710146
  71. [82]Adlard PA, West AK, Vickers JC. Increased density of metallothionein I/II‐immunopositive cortical glial cells in the early stages of Alzheimer's disease. Neurobiol Dis. 1998; 5(5): 349‐ 356. 10069577
  72. [83]Maslinska D, Laure‐Kamionowska M, Maslinski KT, Gujski M, Maslinski S. Distribution of tryptase‐containing mast cells and metallothionein reactive astrocytes in human brains with amyloid deposits. Inflamm Res Off J Eur Histamine Res Soc Al. 2007; 56(Suppl 1): S17‐ S18. 17806161
  73. [84]Uchida Y, Takio K, Titani K, Ihara Y, Tomonaga M. The growth inhibitory factor that is deficient in the Alzheimer's disease brain is a 68 amino acid metallothionein‐like protein. Neuron. 1991; 7(2): 337‐ 347. 1873033
  74. [85]Arai Y, Uchida Y, Takashima S. Developmental immunohistochemistry of growth inhibitory factor in normal brains and brains of patients with Down syndrome. Pediatr Neurol. 1997; 17(2): 134‐ 138. 9367293
  75. [86]Pappolla MA, Omar RA, Kim KS, Robakis NK. Immunohistochemical evidence of oxidative [corrected] stress in Alzheimer's disease. Am J Pathol. 1992; 140(3): 621‐ 628. 1372157 PMC1886174
  76. [87]Furuta A, Price DL, Pardo CA, et al. Localization of superoxide dismutases in Alzheimer's disease and Down's syndrome neocortex and hippocampus. Am J Pathol. 1995; 146(2): 357‐ 367. 7856748 PMC1869844
  77. [88]Schipper HM, Cissé S, Stopa EG. Expression of heme oxygenase‐1 in the senescent and Alzheimer‐diseased brain. Ann Neurol. 1995; 37(6): 758‐ 768. 7778849
  78. [89]Asahina M, Yamada T, Yoshiyama Y, Yodoi J. Expression of adult T cell leukemia‐derived factor in human brain and peripheral nerve tissues. Dement Geriatr Cogn Disord. 1998; 9(4): 181‐ 185. 9681638
  79. [90]Power JHT, Asad S, Chataway TK, et al. Peroxiredoxin 6 in human brain: molecular forms, cellular distribution and association with Alzheimer's disease pathology. Acta Neuropathol (Berl). 2008; 115(6): 611‐ 622. 18386021 PMC2386158
  80. [91]Liu M, Sun A, Shin E‐J, et al. Expression of microsomal epoxide hydrolase is elevated in Alzheimer's hippocampus and induced by exogenous beta‐amyloid and trimethyl‐tin. Eur J Neurosci. 2006; 23(8): 2027‐ 2034. 16630050
  81. [92]Picklo MJ, Olson SJ, Hayes JD, Markesbery WR, Montine TJ. Elevation of AKR7A2 (succinic semialdehyde reductase) in neurodegenerative disease. Brain Res. 2001; 916(1–2): 229‐ 238. 11597610
  82. [93]Namba Y, Tomonaga M, Kawasaki H, Otomo E, Ikeda K. Apolipoprotein E immunoreactivity in cerebral amyloid deposits and neurofibrillary tangles in Alzheimer's disease and kuru plaque amyloid in Creutzfeldt‐Jakob disease. Brain Res. 1991; 541(1): 163‐ 166. 2029618
  83. [94]Diedrich JF, Minnigan H, Carp RI, et al. Neuropathological changes in scrapie and Alzheimer's disease are associated with increased expression of apolipoprotein E and cathepsin D in astrocytes. J Virol. 1991; 65(9): 4759‐ 4768. 1870200 PMC248933
  84. [95]Rebeck GW, Reiter JS, Strickland DK, Hyman BT. Apolipoprotein E in sporadic Alzheimer's disease: allelic variation and receptor interactions. Neuron. 1993; 11(4): 575‐ 580. 8398148
  85. [96]Han SH, Einstein G, Weisgraber KH, et al. Apolipoprotein E is localized to the cytoplasm of human cortical neurons: a light and electron microscopic study. J Neuropathol Exp Neurol. 1994; 53(5): 535‐ 544. 8083695
  86. [97]Han SH, Hulette C, Saunders AM, et al. Apolipoprotein E is present in hippocampal neurons without neurofibrillary tangles in Alzheimer's disease and in age‐matched controls. Exp Neurol. 1994; 128(1): 13‐ 26. 8070517
  87. [98]Harr SD, Uint L, Hollister R, Hyman BT, Mendez AJ. Brain expression of apolipoproteins E, J, and A‐I in Alzheimer's disease. J Neurochem. 1996; 66(6): 2429‐ 2435. 8632166
  88. [99]Uchihara T, Duyckaerts C, He Y, et al. ApoE immunoreactivity and microglial cells in Alzheimer's disease brain. Neurosci Lett. 1995; 195(1): 5‐ 8. 7478253
  89. [100]Shao Y, Gearing M, Mirra SS. Astrocyte‐apolipoprotein E associations in senile plaques in Alzheimer disease and vascular lesions: a regional immunohistochemical study. J Neuropathol Exp Neurol. 1997; 56(4): 376‐ 381. 9100668
  90. [101]Utter S, Tamboli IY, Walter J, et al. Cerebral small vessel disease‐induced apolipoprotein E leakage is associated with Alzheimer disease and the accumulation of amyloid beta‐protein in perivascular astrocytes. J Neuropathol Exp Neurol. 2008; 67(9): 842‐ 856. 18716559
  91. [102]Lidström AM, Bogdanovic N, Hesse C, Volkman I, Davidsson P, Blennow K. Clusterin (apolipoprotein J) protein levels are increased in hippocampus and in frontal cortex in Alzheimer's disease. Exp Neurol. 1998; 154(2): 511‐ 521. 9878186
  92. [103]Troakes C, Smyth R, Noor F, et al. Clusterin expression is upregulated following acute head injury and localizes to astrocytes in old head injury. Neuropathol off J Jpn Soc Neuropathol. 2017; 37(1): 12‐ 24. 27365216
  93. [104]Petit‐Turcotte C, Stohl SM, Beffert U, et al. Apolipoprotein C‐I expression in the brain in Alzheimer's disease. Neurobiol Dis. 2001; 8(6): 953‐ 963. 11741391
  94. [105]Kalman J, McConathy W, Araoz C, Kasa P, Lacko AG. Apolipoprotein D in the aging brain and in Alzheimer's dementia. Neurol Res. 2000; 22(4): 330‐ 336. 10874678
  95. [106]Tooyama I, Kawamata T, Akiyama H, Moestrup SK, Gliemann J, McGeer PL. Immunohistochemical study of alpha 2 macroglobulin receptor in Alzheimer and control postmortem human brain. Mol Chem Neuropathol. 1993; 18(1–2): 153‐ 160. 8466589
  96. [107]Rebeck GW, Harr SD, Strickland DK, Hyman BT. Multiple, diverse senile plaque‐associated proteins are ligands of an apolipoprotein E receptor, the alpha 2‐macroglobulin receptor/low‐density‐lipoprotein receptor‐related protein. Ann Neurol. 1995; 37(2): 211‐ 217. 7531418
  97. [108]Yamada T, Kawata M, Arai H, Fukasawa M, Inoue K, Sato T. Astroglial localization of cholesteryl ester transfer protein in normal and Alzheimer's disease brain tissues. Acta Neuropathol (Berl). 1995; 90(6): 633‐ 636. 8615085
  98. [109]Bogdanovic N, Bretillon L, Lund EG, et al. On the turnover of brain cholesterol in patients with Alzheimer's disease. Abnormal induction of the cholesterol‐catabolic enzyme CYP46 in glial cells. Neurosci Lett. 2001; 314(1–2): 45‐ 48. 11698143
  99. [110]Brown J, Theisler C, Silberman S, et al. Differential expression of cholesterol hydroxylases in Alzheimer's disease. J Biol Chem. 2004; 279(33): 34674‐ 34681. 15148325
  100. [111]Satoi H, Tomimoto H, Ohtani R, et al. Astroglial expression of ceramide in Alzheimer's disease brains: a role during neuronal apoptosis. Neuroscience. 2005; 130(3): 657‐ 666. 15590150
  101. [114]Abraham CR, Shirahama T, Potter H. Alpha 1‐antichymotrypsin is associated solely with amyloid deposits containing the beta‐protein. Amyloid and cell localization of alpha 1‐antichymotrypsin. Neurobiol Aging. 1990; 11(2): 123‐ 129. 2190106
  102. [115]Ishiguro K, Shoji M, Yamaguchi H, et al. Differential expression of alpha 1‐antichymotrypsin in the aged human brain. Virchows Arch B Cell Pathol Incl Mol Pathol. 1993; 64(4): 221‐ 227. 8287118
  103. [116]Styren SD, Kamboh MI, DeKosky ST. Expression of differential immune factors in temporal cortex and cerebellum: the role of alpha‐1‐antichymotrypsin, apolipoprotein E, and reactive glia in the progression of Alzheimer's disease. J Comp Neurol. 1998; 396(4): 511‐ 520. 9651008
  104. [117]Yoshida E, Yoshimura M, Ito Y, Mihara H. Demonstration of an active component of inter‐alpha‐trypsin inhibitor in the brains of Alzheimer type dementia. Biochem Biophys Res Commun. 1991; 174(2): 1015‐ 1021. 1704218
  105. [118]Gilad GM, Kagan HM, Gilad VH. Evidence for increased lysyl oxidase, the extracellular matrix‐forming enzyme, in Alzheimer's disease brain. Neurosci Lett. 2005; 376(3): 210‐ 214. 15721223
  106. [119]Wilhelmus MMM, Bol JGJM, van Duinen SG, Drukarch B. Extracellular matrix modulator lysyl oxidase colocalizes with amyloid‐beta pathology in Alzheimer's disease and hereditary cerebral hemorrhage with amyloidosis—Dutch type. Exp Gerontol. 2013; 48(2): 109‐ 114. 23267843
  107. [120]de Jager M, van der Wildt B, Schul E, et al. Tissue transglutaminase colocalizes with extracellular matrix proteins in cerebral amyloid angiopathy. Neurobiol Aging. 2013; 34(4): 1159‐ 1169. 23122413
  108. [121]Wilhelmus MMM, Grunberg SCS, Bol JGJM, et al. Transglutaminases and transglutaminase‐catalyzed cross‐links colocalize with the pathological lesions in Alzheimer's disease brain. Brain Pathol Zurich Switz. 2009; 19(4): 612‐ 622. PMC8094859 18673368
  109. [122]Yamada T, Yoshiyama Y, Kawaguchi N, et al. Possible roles of transglutaminases in Alzheimer's disease. Dement Geriatr Cogn Disord. 1998; 9(2): 103‐ 110. 9524802
  110. [123]Vogel H, Butcher EC, Picker LJ. H‐CAM expression in the human nervous system: evidence for a role in diverse glial interactions. J Neurocytol. 1992; 21(5): 363‐ 373. 1607880
  111. [124]Akiyama H, Tooyama I, Kawamata T, Ikeda K, McGeer PL. Morphological diversities of CD44 positive astrocytes in the cerebral cortex of normal subjects and patients with Alzheimer's disease. Brain Res. 1993; 632(1–2): 249‐ 259. 7511977
  112. [125]Snow AD, Mar H, Nochlin D, et al. The presence of heparan sulfate proteoglycans in the neuritic plaques and congophilic angiopathy in Alzheimer's disease. Am J Pathol. 1988; 133(3): 456‐ 463. 2974240 PMC1880818
  113. [126]Chaudhury AR, Gerecke KM, Wyss JM, Morgan DG, Gordon MN, Carroll SL. Neuregulin‐1 and erbB4 immunoreactivity is associated with neuritic plaques in Alzheimer disease brain and in a transgenic model of Alzheimer disease. J Neuropathol Exp Neurol. 2003; 62(1): 42‐ 54. 12528817
  114. [127]Pankonin MS, Sohi J, Kamholz J, Loeb JA. Differential distribution of neuregulin in human brain and spinal fluid. Brain Res. 2009; 1258: 1‐ 11. 19150438
  115. [128]Iwamoto N, Suzuki Y, Makino Y, Haga C, Kosaka K, Iizuka R. Cell membrane changes in brains manifesting senile plaques: an immunohistochemical study of GM1 membranous ganglioside. Brain Res. 1990; 522(1): 152‐ 156. 1699633
  116. [129]Nakamura Y, Takeda M, Suzuki H, et al. Abnormal distribution of cathepsins in the brain of patients with Alzheimer's disease. Neurosci Lett. 1991; 130(2): 195‐ 198. 1795881
  117. [130]Cataldo AM, Paskevich PA, Kominami E, Nixon RA. Lysosomal hydrolases of different classes are abnormally distributed in brains of patients with Alzheimer disease. Proc Natl Acad Sci U S a. 1991; 88(24): 10998‐ 11002. 1837142 PMC53060
  118. [131]Kobayashi K, Hayashi M, Nakano H, et al. Apoptosis of astrocytes with enhanced lysosomal activity and oligodendrocytes in white matter lesions in Alzheimer's disease. Neuropathol Appl Neurobiol. 2002; 28(3): 238‐ 251. 12060348
  119. [132]Rohn TT, Wirawan E, Brown RJ, Harris JR, Masliah E, Vandenabeele P. Depletion of Beclin‐1 due to proteolytic cleavage by caspases in the Alzheimer's disease brain. Neurobiol Dis. 2011; 43(1): 68‐ 78. 21081164 PMC3066274
  120. [133]Renkawek K, Voorter CE, Bosman GJ, van Workum FP, de Jong WW. Expression of alpha B‐crystallin in Alzheimer's disease. Acta Neuropathol (Berl). 1994; 87(2): 155‐ 160. 8171966
  121. [134]Wilhelmus MMM, Otte‐Höller I, Wesseling P, de Waal RMW, Boelens WC, Verbeek MM. Specific association of small heat shock proteins with the pathological hallmarks of Alzheimer's disease brains. Neuropathol Appl Neurobiol. 2006; 32(2): 119‐ 130. 16599941
  122. [135]Bruinsma IB, de Jager M, Carrano A, et al. Small heat shock proteins induce a cerebral inflammatory reaction. J Neurosci off J Soc Neurosci. 2011; 31(33): 11992‐ 12000. PMC6623184 21849559
  123. [136]Renkawek K, Bosman GJ, Gaestel M. Increased expression of heat‐shock protein 27 kDa in Alzheimer disease: a preliminary study. Neuroreport. 1993; 5(1): 14‐ 16. 8280851
  124. [137]Rizzu P, Hinkle DA, Zhukareva V, et al. DJ‐1 colocalizes with tau inclusions: a link between parkinsonism and dementia. Ann Neurol. 2004; 55(1): 113‐ 118. 14705119
  125. [138]Witte ME, Bol JGJM, Gerritsen WH, et al. Parkinson's disease‐associated parkin colocalizes with Alzheimer's disease and multiple sclerosis brain lesions. Neurobiol Dis. 2009; 36(3): 445‐ 452. 19716418
  126. [139]Hou H‐L, Shen Y‐X, Zhu H‐Y, et al. Alterations of hHrd1 expression are related to hyperphosphorylated tau in the hippocampus in Alzheimer's disease. J Neurosci Res. 2006; 84(8): 1862‐ 1870. 17044033
  127. [140]Garwood C, Faizullabhoy A, Wharton SB, et al. Calcium dysregulation in relation to Alzheimer‐type pathology in the ageing brain. Neuropathol Appl Neurobiol. 2013; 39(7): 788‐ 799. 23421725
  128. [141]Hannula MJ, Myöhänen TT, Tenorio‐Laranga J, Männistö PT, Garcia‐Horsman JA. Prolyl oligopeptidase colocalizes with α‐synuclein, β‐amyloid, tau protein and astroglia in the post‐mortem brain samples with Parkinson's and Alzheimer's diseases. Neuroscience. 2013; 242: 140‐ 150. 23562579
  129. [142]Tumani H, Shen G, Peter JB, Brück W. Glutamine synthetase in cerebrospinal fluid, serum, and brain: a diagnostic marker for Alzheimer disease? Arch Neurol. 1999; 56(10): 1241‐ 1246. 10520940
  130. [143]Fluteau A, Ince PG, Minett T, et al. The nuclear retention of transcription factor FOXO3a correlates with a DNA damage response and increased glutamine synthetase expression by astrocytes suggesting a neuroprotective role in the ageing brain. Neurosci Lett. 2015; 609: 11‐ 17. 26455863 PMC4674771
  131. [144]Robinson SR. Neuronal expression of glutamine synthetase in Alzheimer's disease indicates a profound impairment of metabolic interactions with astrocytes. Neurochem Int. 2000; 36(4–5): 471‐ 482. 10733015
  132. [145]Robinson SR. Changes in the cellular distribution of glutamine synthetase in Alzheimer's disease. J Neurosci Res. 2001; 66(5): 972‐ 980. 11746426
  133. [147]Li S, Mallory M, Alford M, Tanaka S, Masliah E. Glutamate transporter alterations in Alzheimer disease are possibly associated with abnormal APP expression. J Neuropathol Exp Neurol. 1997; 56(8): 901‐ 911. 9258260
  134. [148]Simpson JE, Ince PG, Lace G, et al. Astrocyte phenotype in relation to Alzheimer‐type pathology in the ageing brain. Neurobiol Aging. 2010; 31(4): 578‐ 590. 18586353
  135. [150]Casley CS, Lakics V, Lee H, et al. Up‐regulation of astrocyte metabotropic glutamate receptor 5 by amyloid‐β peptide. Brain Res. 2009; 1260: 65‐ 75. 19401173
  136. [151]Iyer AM, van Scheppingen J, Milenkovic I, et al. Metabotropic glutamate receptor 5 in Down's syndrome hippocampus during development: increased expression in astrocytes. Curr Alzheimer Res. 2014; 11(7): 694‐ 705. 25115540
  137. [152]Balu DT, Pantazopoulos H, Huang CCY, et al. Neurotoxic astrocytes express the d‐serine synthesizing enzyme, serine racemase, in Alzheimer's disease. Neurobiol Dis. 2019; 130: 104511. 31212068 PMC6689433
  138. [154]Jo S, Yarishkin O, Hwang YJ, et al. GABA from reactive astrocytes impairs memory in mouse models of Alzheimer's disease. Nat Med. 2014; 20(8): 886‐ 896. 24973918 PMC8385452
  139. [155]Wevers A, Monteggia L, Nowacki S, et al. Expression of nicotinic acetylcholine receptor subunits in the cerebral cortex in Alzheimer's disease: histotopographical correlation with amyloid plaques and hyperphosphorylated‐tau protein. Eur J Neurosci. 1999; 11(7): 2551‐ 2565. 10383644
  140. [157]Teaktong T, Graham AJ, Court JA, et al. Nicotinic acetylcholine receptor immunohistochemistry in Alzheimer's disease and dementia with Lewy bodies: differential neuronal and astroglial pathology. J Neurol Sci. 2004; 225(1–2): 39‐ 49. 15465084
  141. [158]Nagele RG, D'Andrea MR, Lee H, Venkataraman V, Wang H‐Y. Astrocytes accumulate A beta 42 and give rise to astrocytic amyloid plaques in Alzheimer disease brains. Brain Res. 2003; 971(2): 197‐ 209. 12706236
  142. [159]Yu W‐F, Guan Z‐Z, Bogdanovic N, Nordberg A. High selective expression of alpha7 nicotinic receptors on astrocytes in the brains of patients with sporadic Alzheimer's disease and patients carrying Swedish APP 670/671 mutation: a possible association with neuritic plaques. Exp Neurol. 2005; 192(1): 215‐ 225. 15698636
  143. [160]Messamore E, Bogdanovich N, Schröder H, Winblad B. Astrocytes associated with senile plaques possess muscarinic acetylcholine receptors. Neuroreport. 1994; 5(12): 1473‐ 1476. 7948841
  144. [161]Kumar U, Patel SC. Immunohistochemical localization of dopamine receptor subtypes (D1R‐D5R) in Alzheimer's disease brain. Brain Res. 2007; 1131(1): 187‐ 196. 17182012
  145. [162]Wu C, Singh SK, Dias P, Kumar S, Mann DM. Activated astrocytes display increased 5‐HT2a receptor expression in pathological states. Exp Neurol. 1999; 158(2): 529‐ 533. 10415157
  146. [163]Guillemin GJ, Brew BJ, Noonan CE, Takikawa O, Cullen KM. Indoleamine 2,3 dioxygenase and quinolinic acid immunoreactivity in Alzheimer's disease hippocampus. Neuropathol Appl Neurobiol. 2005; 31(4): 395‐ 404. 16008823
  147. [164]Orr AG, Hsiao EC, Wang MM, et al. Astrocytic adenosine receptor A2A and Gs‐coupled signaling regulate memory. Nat Neurosci. 2015; 18(3): 423‐ 434. 25622143 PMC4340760
  148. [165]Yamada T, Tsubouchi H, Daikuhara Y, et al. Immunohistochemistry with antibodies to hepatocyte growth factor and its receptor protein (c‐MET) in human brain tissues. Brain Res. 1994; 637(1–2): 308‐ 312. 8180811
  149. [166]Fenton H, Finch PW, Rubin JS, et al. Hepatocyte growth factor (HGF/SF) in Alzheimer's disease. Brain Res. 1998; 779(1–2): 262‐ 270. 9473690
  150. [167]Yamada T, Yoshiyama Y, Tsuboi Y, Shimomura T. Astroglial expression of hepatocyte growth factor and hepatocyte growth factor activator in human brain tissues. Brain Res. 1997; 762(1–2): 251‐ 255. 9262185
  151. [168]Tooyama I, Akiyama H, McGeer PL, Hara Y, Yasuhara O, Kimura H. Acidic fibroblast growth factor‐like immunoreactivity in brain of Alzheimer patients. Neurosci Lett. 1991; 121(1–2): 155‐ 158. 1708473
  152. [169]Kimura H, Tooyama I, McGeer PL. Acidic FGF expression in the surroundings of senile plaques. Tohoku J Exp Med. 1994; 174(3): 279‐ 293. 7539161
  153. [170]Gómez‐Pinilla F, Cummings BJ, Cotman CW. Induction of basic fibroblast growth factor in Alzheimer's disease pathology. Neuroreport. 1990; 1(3–4): 211‐ 214. 1717039
  154. [171]Stopa EG, Gonzalez AM, Chorsky R, et al. Basic fibroblast growth factor in Alzheimer's disease. Biochem Biophys Res Commun. 1990; 171(2): 690‐ 696. 2403357
  155. [172]Cummings BJ, Su JH, Cotman CW. Neuritic involvement within bFGF immunopositive plaques of Alzheimer's disease. Exp Neurol. 1993; 124(2): 315‐ 325. 8287930
  156. [173]Pike CJ, Cummings BJ, Monzavi R, Cotman CW. Beta‐amyloid‐induced changes in cultured astrocytes parallel reactive astrocytosis associated with senile plaques in Alzheimer's disease. Neuroscience. 1994; 63(2): 517‐ 531. 7891862
  157. [174]Takami K, Matsuo A, Terai K, Walker DG, McGeer EG, McGeer PL. Fibroblast growth factor receptor‐1 expression in the cortex and hippocampus in Alzheimer's disease. Brain Res. 1998; 802(1–2): 89‐ 97. 9748519
  158. [175]Flanders KC, Lippa CF, Smith TW, Pollen DA, Sporn MB. Altered expression of transforming growth factor‐beta in Alzheimer's disease. Neurology. 1995; 45(8): 1561‐ 1569. 7543987
  159. [176]Peress NS, Perillo E. Differential expression of TGF‐beta 1, 2 and 3 isotypes in Alzheimer's disease: a comparative immunohistochemical study with cerebral infarction, aged human and mouse control brains. J Neuropathol Exp Neurol. 1995; 54(6): 802‐ 811. 7595653
  160. [177]Tashiro H, Dohura K, Iwaki T. Differential expression of transforming growth factor‐beta isoforms in human prion diseases. Neuropathol Appl Neurobiol. 1998; 24(4): 284‐ 292. 9775394
  161. [178]de la Monte SM, Ng SC, Hsu DW. Aberrant GAP‐43 gene expression in Alzheimer's disease. Am J Pathol. 1995; 147(4): 934‐ 946. 7573369 PMC1871017
  162. [179]Rensink AAM, Gellekink H, Otte‐Höller I, et al. Expression of the cytokine leukemia inhibitory factor and pro‐apoptotic insulin‐like growth factor binding protein‐3 in Alzheimer's disease. Acta Neuropathol (Berl). 2002; 104(5): 525‐ 533. 12410400
  163. [180]Thomason LAM, Smithson LJ, Hazrati L‐N, McLaurin J, Kawaja MD. Reactive astrocytes associated with plaques in TgCRND8 mouse brain and in human Alzheimer brain express phosphoprotein enriched in astrocytes (PEA‐15). FEBS Lett. 2013; 587(15): 2448‐ 2454. 23792157
  164. [181]O'Barr S, Schultz J, Rogers J. Expression of the protooncogene bcl‐2 in Alzheimer's disease brain. Neurobiol Aging. 1996; 17(1): 131‐ 136. 8786795
  165. [182]Kobayashi K, Hayashi M, Nakano H, Shimazaki M, Sugimori K, Koshino Y. Correlation between astrocyte apoptosis and Alzheimer changes in gray matter lesions in Alzheimer's disease. J Alzheimers Dis JAD. 2004; 6(6): 623‐ 632. discussion 673‐681 15665402
  166. [183]Ferrer I, Blanco R. N‐myc and c‐myc expression in Alzheimer disease, Huntington disease and Parkinson disease. Brain Res Mol Brain Res. 2000; 77(2): 270‐ 276. 10837922
  167. [185]Ueberham U, Hessel A, Arendt T. Cyclin C expression is involved in the pathogenesis of Alzheimer's disease. Neurobiol Aging. 2003; 24(3): 427‐ 435. 12600719
  168. [186]Tsujioka Y, Takahashi M, Tsuboi Y, Yamamoto T, Yamada T. Localization and expression of cdc2 and cdk4 in Alzheimer brain tissue. Dement Geriatr Cogn Disord. 1999; 10(3): 192‐ 198. 10325446
  169. [187]Vincent I, Jicha G, Rosado M, Dickson DW. Aberrant expression of mitotic cdc2/cyclin B1 kinase in degenerating neurons of Alzheimer's disease brain. J Neurosci off J Soc Neurosci. 1997; 17(10): 3588‐ 3598. PMC6573674 9133382
  170. [188]de la Monte SM, Sohn YK, Wands JR. Correlates of p53‐ and Fas (CD95)‐mediated apoptosis in Alzheimer's disease. J Neurol Sci. 1997; 152(1): 73‐ 83. 9395128
  171. [189]Jordan‐Sciutto KL, Malaiyandi LM, Bowser R. Altered distribution of cell cycle transcriptional regulators during Alzheimer disease. J Neuropathol Exp Neurol. 2002; 61(4): 358‐ 367. 11939591 PMC3683585
  172. [190]Previll LA, Crosby ME, Castellani RJ, et al. Increased expression of p130 in Alzheimer disease. Neurochem Res. 2007; 32(4–5): 639‐ 644. 17006760
  173. [191]Leroy K, Duyckaerts C, Bovekamp L, Müller O, Anderton BH, Brion JP. Increase of adenomatous polyposis coli immunoreactivity is a marker of reactive astrocytes in Alzheimer's disease and in other pathological conditions. Acta Neuropathol (Berl). 2001; 102(1): 1‐ 10. 11547943
  174. [192]Sonoda Y, Mukai H, Matsuo K, et al. Accumulation of tumor‐suppressor PTEN in Alzheimer neurofibrillary tangles. Neurosci Lett. 2010; 471(1): 20‐ 24. 20056128
  175. [193]Turnquist C, Horikawa I, Foran E, et al. p53 isoforms regulate astrocyte‐mediated neuroprotection and neurodegeneration. Cell Death Differ. 2016; 23(9): 1515‐ 1528. 27104929 PMC5072428
  176. [194]Verwer RWH, Sluiter AA, Balesar RA, et al. Mature astrocytes in the adult human neocortex express the early neuronal marker doublecortin. Brain J Neurol. 2007; 130(Pt 12): 3321‐ 3335. 18055496
  177. [195]Su JH, Zhao M, Anderson AJ, Srinivasan A, Cotman CW. Activated caspase‐3 expression in Alzheimer's and aged control brain: correlation with Alzheimer pathology. Brain Res. 2001; 898(2): 350‐ 357. 11306022
  178. [196]Nishimura T, Akiyama H, Yonehara S, et al. Fas antigen expression in brains of patients with Alzheimer‐type dementia. Brain Res. 1995 Oct 16; 695(2): 137‐ 145. 8556323
  179. [197]Ferrer I, Puig B, Krupinsk J, Carmona M, Blanco R. Fas and Fas ligand expression in Alzheimer's disease. Acta Neuropathol (Berl). 2001; 102(2): 121‐ 131. 11563626
  180. [198]Smale G, Nichols NR, Brady DR, Finch CE, Horton WE. Evidence for apoptotic cell death in Alzheimer's disease. Exp Neurol. 1995; 133(2): 225‐ 230. 7544290
  181. [199]Li WP, Chan WY, Lai HW, Yew DT. Terminal dUTP nick end labeling (TUNEL) positive cells in the different regions of the brain in normal aging and Alzheimer patients. J Mol Neurosci MN. 1997; 8(2): 75‐ 82. 9188038
  182. [200]López‐González I, Carmona M, Blanco R, et al. Characterization of thorn‐shaped astrocytes in white matter of temporal lobe in Alzheimer's disease brains. Brain Pathol Zurich Switz. 2013; 23(2): 144‐ 153. PMC8028879 22882361
  183. [201]Webster B, Hansen L, Adame A, et al. Astroglial activation of extracellular‐regulated kinase in early stages of Alzheimer disease. J Neuropathol Exp Neurol. 2006; 65(2): 142‐ 151. 16462205
  184. [202]Rosenberger AFN, Morrema THJ, Gerritsen WH, et al. Increased occurrence of protein kinase CK2 in astrocytes in Alzheimer's disease pathology. J Neuroinflammation. 2016; 13: 4. 26732432 PMC4702323
  185. [203]Lee C, Low CYB, Francis PT, et al. An isoform‐specific role of FynT tyrosine kinase in Alzheimer's disease. J Neurochem. 2016; 136(3): 637‐ 650. 26561212
  186. [204]Pei JJ, Grundke‐Iqbal I, Iqbal K, Bogdanovic N, Winblad B, Cowburn RF. Elevated protein levels of protein phosphatases PP‐2A and PP‐2B in astrocytes of Alzheimer's disease temporal cortex. J Neural Transm Vienna Austria 1996. 1997; 104(11–12): 1329‐ 1338. 9503279
  187. [205]Watanabe K, Uemura K, Asada M, et al. The participation of insulin‐like growth factor‐binding protein 3 released by astrocytes in the pathology of Alzheimer's disease. Mol Brain. 2015; 8(1): 82. 26637371 PMC4670528
  188. [206]Pleiss MM, Sompol P, Kraner SD, et al. Calcineurin proteolysis in astrocytes: implications for impaired synaptic function. Biochim Biophys Acta. 2016; 1862(9): 1521‐ 1532. 27212416 PMC5026189
  189. [207]Byman E, Schultz N, Netherlands Brain Bank, Fex M, Wennström M. Brain alpha‐amylase: a novel energy regulator important in Alzheimer disease? Brain Pathol Zurich Switz. 2018; 28(6): 920‐ 932. PMC8028266 29485701
  190. [208]Connor B, Beilharz EJ, Williams C, et al. Insulin‐like growth factor‐I (IGF‐I) immunoreactivity in the Alzheimer's disease temporal cortex and hippocampus. Brain Res Mol Brain Res. 1997; 49(1–2): 283‐ 290. 9387889
  191. [209]Jafferali S, Dumont Y, Sotty F, Robitaille Y, Quirion R, Kar S. Insulin‐like growth factor‐I and its receptor in the frontal cortex, hippocampus, and cerebellum of normal human and alzheimer disease brains. Synap N Y N. 2000; 38(4): 450‐ 459. 11044892
  192. [210]Moloney AM, Griffin RJ, Timmons S, O'Connor R, Ravid R, O'Neill C. Defects in IGF‐1 receptor, insulin receptor and IRS‐1/2 in Alzheimer's disease indicate possible resistance to IGF‐1 and insulin signalling. Neurobiol Aging. 2010; 31(2): 224‐ 243. 18479783
  193. [211]Kar S, Poirier J, Guevara J, et al. Cellular distribution of insulin‐like growth factor‐II/mannose‐6‐phosphate receptor in normal human brain and its alteration in Alzheimer's disease pathology. Neurobiol Aging. 2006; 27(2): 199‐ 210. 16399207
  194. [212]Nakamura Y, Takeda M, Yoshimi K, et al. Involvement of clathrin light chains in the pathology of Alzheimer's disease. Acta Neuropathol (Berl). 1994; 87(1): 23‐ 31. 8140893
  195. [213]Herrmann L, Wiegmann C, Arsalan‐Werner A, et al. Hook proteins: association with Alzheimer pathology and regulatory role of hook3 in amyloid beta generation. PloS One. 2015; 10(3): e0119423. 25799409 PMC4370497
  196. [214]Kreft KL, van Meurs M, Wierenga‐Wolf AF, et al. Abundant kif21b is associated with accelerated progression in neurodegenerative diseases. Acta Neuropathol Commun. 2014; 2: 144. 25274010 PMC4207309
  197. [215]Plá V, Paco S, Ghezali G, et al. Secretory sorting receptors carboxypeptidase E and secretogranin III in amyloid β‐associated neural degeneration in Alzheimer's disease. Brain Pathol Zurich Switz. 2013; 23(3): 274‐ 284. PMC8028878 22998035
  198. [216]Jiang MH, Höög A, Ma KC, Nie XJ, Olsson Y, Zhang WW. Endothelin‐1‐like immunoreactivity is expressed in human reactive astrocytes. Neuroreport. 1993; 4(7): 935‐ 937. 8369484
  199. [217]Zhang WW, Badonic T, Höög A, et al. Astrocytes in Alzheimer's disease express immunoreactivity to the vaso‐constrictor endothelin‐1. J Neurol Sci. 1994; 122(1): 90‐ 96. 8195809
  200. [218]Romanitan MO, Popescu BO, Spulber S, et al. Altered expression of claudin family proteins in Alzheimer's disease and vascular dementia brains. J Cell Mol Med. 2010; 14(5): 1088‐ 1100. 20041969 PMC3822746

200 of 270 shown

Cited by

Sorted by citations

Authors
Viejo, L., Noori, A., Merrill, E., Das, S., Hyman, B. T., & Serrano‐Pozo, A.
Affiliations
  • Massachusetts General Hospital (US)
  • Harvard University (US)
Corresponding author
Serrano‐Pozo, Alberto
ORCID
Venue
Neuropathology and Applied Neurobiology
Publisher
Wiley
Published
2021-08-17
Volume
48
Issue
1
Pages
e12753-e12753
ISSN
  • 0305-1846 (ISSN-L)
  • 1365-2990
DOI
10.1111/nan.12753
PMC
PMC8766893
OpenAlex
W3185758573
Cited by
69
References
24
Citations by year
2026: 6 · 2025: 13 · 2024: 13 · 2023: 18 · 2022: 16 · 2021: 2
FWCI
1.70
Type
journal article
Language
en
Open access
Licence
Locations
  • Neuropathology and Applied Neurobiology (publishedVersion, cc-by-nc-nd)
  • PubMed Central (publishedVersion, cc-by-nc-nd)
  • PubMed (publishedVersion)
Funders
  • Alzheimer's Association
  • JPB Foundation
  • National Institute on Aging
  • Ministerio de Ciencia e Innovación
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, reactive astrogliosis, astrocytes, glial fibrillary acidic protein, astrocyte markers, neuroinflammation, oxidative stress, antioxidant defense, lipid metabolism, proteostasis, extracellular matrix, neurotransmission, CTCF, ESR1, transcription factors
MeSH terms
Alzheimer Disease, Astrocytes, Gliosis, Humans, Computational Biology, Proteomics

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review