CoChat
Sign Up
Cited by 77Neuroinflammation and Neurodegeneration MechanismsAlzheimer's disease research and treatmentsNeurological Disease Mechanisms and Treatments

Elucidating the interactive roles of glia in Alzheimer’s disease using established and newly developed experimental models

Open access
Chun, Heejung, Marriott, Ian, Lee, C. Justin, Cho, Hansang·2018·Frontiers in Neurology
DOI 10.3389/fneur.2018.00797PMC PMC6168676
Open this paper in CoChat — free accountOpen PDF

Abstract

Alzheimer’s disease (AD) is an irreversible neurodegenerative illness and the exact etiology of the disease remains unknown. It is characterized by long preclinical and prodromal phases with pathological features including an accumulation of amyloid-beta (Aβ) peptides into extracellular Aβ plaques in the brain parenchyma and the formation of intracellular neurofibrillary tangles (NFTs) within neurons as a result of abnormal phosphorylation of microtubule-associated tau proteins. In addition, prominent activation of innate immune cells is also observed and/or followed by marked neuroinflammation. While such neuroinflammatory responses may function in a neuroprotective manner by clearing neurotoxic factors, they can also be neurotoxic by contributing to neurodegeneration via elevated levels of proinflammatory mediators and oxidative stress, and altered levels of neurotransmitters, that underlie pathological symptoms including synaptic and cognitive impairment, neuronal death, reduced memory, and neocortex and hippocampus malfunctions. Glial cells, particularly activated microglia and reactive astrocytes appear to play critical and interactive roles in such dichotomous responses. Accumulating evidence clearly point to their critical involvement in the prevention, initiation, and progression, of neurodegenerative diseases, including AD. Here, we review recent findings on the roles of astrocyte-microglial interactions in neurodegeneration in the context of AD and discuss newly developed in vitro and in vivo experimental models that will enable more detailed analysis of glial interplay. An increased understanding of the roles of glia and the development of new exploratory tools are likely to be crucial for the development of new interventions for early stage AD prevention and cures.

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 · 10.3389/fneur.2018.00797

Cites

25 of 25 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?

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: 66

  1. [2]Hawkes N. Merck ends trial of potential Alzheimer's drug verubecestat. BMJ (2017) 356: j845. 10.1136/bmj.j845 28202490 · DOI
  2. [3]Jack CR Jr Knopman DS Jagust WJ Shaw LM Aisen PS Weiner MW. Hypothetical model of dynamic biomarkers of the Alzheimer's pathological cascade. Lancet Neurol. (2010) 9: 119– 28. 10.1016/S1474-4422(09)70299-6 20083042 PMC2819840 · DOI · Paper page
  3. [4]Morimoto K Horio J Satoh H Sue L Beach T Arita S. Expression profiles of cytokines in the brains of Alzheimer's disease (AD) patients compared to the brains of non-demented patients with and without increasing AD pathology. J Alzheimers Dis. (2011) 25: 59– 76. 10.3233/JAD-2011-101815 21368376 PMC3572941 · DOI
  4. [5]Lichtenstein MP Carriba P Masgrau R Pujol A Galea E. Staging anti-inflammatory therapy in Alzheimer's disease. Front Aging Neurosci. (2010) 2: 142. 10.3389/fnagi.2010.00142 21152343 PMC2998033 · DOI
  5. [6]Szekely CA Zandi PP. Non-steroidal anti-inflammatory drugs and Alzheimer's disease: the epidemiological evidence. CNS Neurol Disord Drug Targets (2010) 9: 132– 9. 10.2174/187152710791012026 20205647 · DOI
  6. [7]Cagnin A Brooks DJ Kennedy AM Gunn RN Myers R Turkheimer FE. In-vivo measurement of activated microglia in dementia. Lancet (2001) 358: 461– 7. 10.1016/S0140-6736(01)05625-2 11513911 · DOI · Paper page
  7. [8]Parachikova A Agadjanyan MG Cribbs DH Blurton-Jones M Perreau V Rogers J. Inflammatory changes parallel the early stages of Alzheimer disease. Neurobiol Aging (2007) 28: 1821– 33. 10.1016/j.neurobiolaging.2006.08.014 17052803 PMC2198930 · DOI · Paper page
  8. [9]Sofroniew MV. Molecular dissection of reactive astrogliosis and glial scar formation. Trends Neurosci. (2009) 32: 638– 47. 10.1016/j.tins.2009.08.002 19782411 PMC2787735 · DOI · Paper page
  9. [11]Graeber MB. Changing face of microglia. Science (2010) 330: 783– 8. 10.1126/science.1190929 21051630 · DOI · Paper page
  10. [12]Kettenmann H Hanisch UK Noda M Verkhratsky A. Physiology of microglia. Physiol Rev. (2011) 91: 461– 553. 10.1152/physrev.00011.2010 21527731 · DOI · Paper page
  11. [13]Aguzzi A Barres BA Bennett ML Microglia: scapegoat, saboteur, or something else? Science (2013) 339: 156– 61. 10.1126/science.1227901 23307732 PMC4431634 · DOI · Paper page
  12. [14]Li Q Barres BA. Microglia and macrophages in brain homeostasis and disease. Nat Rev Immunol. (2018) 18: 225– 42. 10.1038/nri.2017.125 29151590 · DOI · Paper page
  13. [16]Ransohoff RM. A polarizing question: do M1 and M2 microglia exist? Nat Neurosci (2016) 19: 987– 91. 10.1038/nn.4338 27459405 · DOI · Paper page
  14. [17]Benzing WC Wujek JR Ward EK Shaffer D Ashe KH Younkin SG. Evidence for glial-mediated inflammation in aged APP(SW) transgenic mice. Neurobiol Aging (1999) 20: 581– 9. 10.1016/S0197-4580(99)00065-2 10674423 · DOI
  15. [18]Bornemann KD Wiederhold KH Pauli C Ermini F Stalder M Schnell L. Abeta-induced inflammatory processes in microglia cells of APP23 transgenic mice. Am J Pathol. (2001) 158: 63– 73. 10.1016/S0002-9440(10)63945-4 11141480 PMC1850262 · DOI
  16. [19]Heneka MT Sastre M Dumitrescu-Ozimek L Dewachter I Walter J Klockgether T. Focal glial activation coincides with increased BACE1 activation and precedes amyloid plaque deposition in APP[V717I] transgenic mice. J Neuroinflamm. (2005) 2: 22. 10.1186/1742-2094-2-22 16212664 PMC1274341 · DOI · Paper page
  17. [21]Bellucci A Westwood AJ Ingram E Casamenti F Goedert M Spillantini MG. Induction of inflammatory mediators and microglial activation in mice transgenic for mutant human P301S tau protein. Am J Pathol. (2004) 165: 1643– 52. 10.1016/S0002-9440(10)63421-9 15509534 PMC1618683 · DOI
  18. [23]Jo S Yarishkin O Hwang YJ Chun YE Park M Woo DH. GABA from reactive astrocytes impairs memory in mouse models of Alzheimer's disease. Nat Med. (2014) 20: 886– 96. 10.1038/nm.3639 24973918 PMC8385452 · DOI · Paper page
  19. [24]Abbas N Bednar I Mix E Marie S Paterson D Ljungberg A. Up-regulation of the inflammatory cytokines IFN-gamma and IL-12 and down-regulation of IL-4 in cerebral cortex regions of APP(SWE) transgenic mice. J Neuroimmunol. (2002) 126: 50– 7. 10.1016/S0165-5728(02)00050-4 12020956 · DOI
  20. [25]Patel NS Paris D Mathura V Quadros AN Crawford FC Mullan MJ. Inflammatory cytokine levels correlate with amyloid load in transgenic mouse models of Alzheimer's disease. J Neuroinflamm. (2005) 2: 9. 10.1186/1742-2094-2-9 15762998 PMC555557 · DOI
  21. [26]Vom Berg J Prokop S Miller KR Obst J Kalin RE Lopategui-Cabezas I. Inhibition of IL-12/IL-23 signaling reduces Alzheimer's disease-like pathology and cognitive decline. Nat Med. (2012) 18: 1812– 9. 10.1038/nm.2965 23178247 · DOI · Paper page
  22. [27]Liang X Wang Q Hand T Wu L Breyer RM Montine TJ. Deletion of the prostaglandin E2 EP2 receptor reduces oxidative damage and amyloid burden in a model of Alzheimer's disease. J Neurosci. (2005) 25: 10180– 7. 10.1523/JNEUROSCI.3591-05.2005 16267225 PMC6725803 · DOI
  23. [30]Irizarry MC Soriano F Mcnamara M Page KJ Schenk D Games D Abeta deposition is associated with neuropil changes, but not with overt neuronal loss in the human amyloid precursor protein V717F (PDAPP) transgenic mouse. J Neurosci. (1997) 17: 7053– 9. 9278541 PMC6573263
  24. [31]Oddo S Caccamo A Shepherd JD Murphy MP Golde TE Kayed R. Triple-transgenic model of Alzheimer's disease with plaques and tangles: intracellular Abeta and synaptic dysfunction. Neuron (2003) 39: 409– 21. 10.1016/S0896-6273(03)00434-3 12895417 · DOI · Paper page
  25. [32]Wirths O Bayer TA. Neuron loss in transgenic mouse models of Alzheimer's disease. Int J Alzheimers Dis. (2010) 2010: 723782. 10.4061/2010/723782 20871861 PMC2943100 · DOI
  26. [35]Von Bernhardi R Eugenin J. Microglial reactivity to beta-amyloid is modulated by astrocytes and proinflammatory factors. Brain Res. (2004) 1025: 186– 93. 10.1016/j.brainres.2004.07.084 15464759 · DOI
  27. [36]Eyupoglu IY Bechmann I Nitsch R. Modification of microglia function protects from lesion-induced neuronal alterations and promotes sprouting in the hippocampus. FASEB J. (2003) 17: 1110– 1. 10.1096/fj.02-0825fje 12692086 · DOI
  28. [37]Colangelo V Schurr J Ball MJ Pelaez RP Bazan NG Lukiw WJ. Gene expression profiling of 12633 genes in Alzheimer hippocampal CA1: transcription and neurotrophic factor down-regulation and up-regulation of apoptotic and pro-inflammatory signaling. J Neurosci Res. (2002) 70: 462– 73. 10.1002/jnr.10351 12391607 · DOI · Paper page
  29. [38]Saud K Herrera-Molina R Von Bernhardi R. Pro- and anti-inflammatory cytokines regulate the ERK pathway: implication of the timing for the activation of microglial cells. Neurotox Res. (2005) 8: 277– 87. 10.1007/BF03033981 16371322 · DOI
  30. [39]Zhu Y Culmsee C Klumpp S Krieglstein J. Neuroprotection by transforming growth factor-beta1 involves activation of nuclear factor-kappaB through phosphatidylinositol-3-OH kinase/Akt and mitogen-activated protein kinase-extracellular-signal regulated kinase1,2 signaling pathways. Neuroscience (2004) 123: 897– 906. 10.1016/j.neuroscience.2003.10.037 14751283 · DOI
  31. [40]Furman JL Sama DM Gant JC Beckett TL Murphy MP Bachstetter AD. Targeting astrocytes ameliorates neurologic changes in a mouse model of Alzheimer's disease. J Neurosci. (2012) 32: 16129– 40. 10.1523/JNEUROSCI.2323-12.2012 23152597 PMC3506017 · DOI · Paper page
  32. [43]Lian H Litvinchuk A Chiang AC Aithmitti N Jankowsky JL Zheng H. Astrocyte-microglia cross talk through complement activation modulates amyloid pathology in mouse models of alzheimer's disease. J Neurosci. (2016) 36: 577– 89. 10.1523/JNEUROSCI.2117-15.2016 26758846 PMC4710776 · DOI · Paper page
  33. [44]Bialas AR Presumey J Das A Van Der Poel CE Lapchak PH Mesin L. Microglia-dependent synapse loss in type I interferon-mediated lupus. Nature (2017) 546: 539– 43. 10.1038/nature22821 28614301 · DOI · Paper page
  34. [45]Dissing-Olesen L Ledue JM Rungta RL Hefendehl JK Choi HB Macvicar BA. Activation of neuronal NMDA receptors triggers transient ATP-mediated microglial process outgrowth. J Neurosci. (2014) 34: 10511– 27. 10.1523/JNEUROSCI.0405-14.2014 25100586 PMC6802598 · DOI · Paper page
  35. [46]Davalos D Grutzendler J Yang G Kim JV Zuo Y Jung S. ATP mediates rapid microglial response to local brain injury in vivo. Nat Neurosci. (2005) 8: 752– 8. 10.1038/nn1472 15895084 · DOI · Paper page
  36. [50]Emilsson L Saetre P Balciuniene J Castensson A Cairns N Jazin EE. Increased monoamine oxidase messenger RNA expression levels in frontal cortex of Alzheimer's disease patients. Neurosci Lett. (2002) 326: 56– 60. 10.1016/S0304-3940(02)00307-5 12052537 · DOI
  37. [51]Borroni E Bohrmann B Grueninger F Prinssen E Nave S Loetscher H. Sembragiline: a novel, selective monoamine oxidase type b inhibitor for the treatment of alzheimer's disease. J Pharmacol Exp Ther. (2017) 362: 413– 23. 10.1124/jpet.117.241653 28642233 · DOI
  38. [52]Deatly AM Haase AT Fewster PH Lewis E Ball MJ. Human herpes virus infections and Alzheimer's disease. Neuropathol Appl Neurobiol. (1990) 16: 213– 23. 10.1111/j.1365-2990.1990.tb01158.x 2169597 · DOI
  39. [53]Itabashi S Arai H Matsui T Higuchi S Sasaki H. Herpes simplex virus and risk of Alzheimer's disease. Lancet (1997). 349: 1102. 10.1016/S0140-6736(05)62325-2 9107270 · DOI
  40. [54]Eimer WA Vijaya Kumar DK Navalpur Shanmugam NK Rodriguez AS Mitchell T Washicosky KJ. (2018). Alzheimer's disease-associated beta-amyloid is rapidly seeded by herpesviridae to protect against brain infection. Neuron 99: 56– 63 e53. 10.1016/j.neuron.2018.06.030 30001512 PMC6075814 · DOI · Paper page
  41. [55]Ma KC Nie XJ Hoog A Olsson Y Zhang WW. Reactive astrocytes in viral infections of the human brain express endothelin-like immunoreactivity. J Neurol Sci. (1994) 126: 184– 92. 10.1016/0022-510X(94)90271-2 7531760 · DOI
  42. [56]Chen J Yang YF Yang Y Zou P Chen J He Y. AXL promotes Zika virus infection in astrocytes by antagonizing type I interferon signalling. Nat Microbiol. (2018) 3: 302– 9. 10.1038/s41564-017-0092-4 29379210 · DOI
  43. [57]Piacentini R Li Puma DD Ripoli C Marcocci ME De Chiara G Garaci E. Herpes Simplex Virus type-1 infection induces synaptic dysfunction in cultured cortical neurons via GSK-3 activation and intraneuronal amyloid-beta protein accumulation. Sci Rep. (2015) 5: 15444. 10.1038/srep15444 26487282 PMC4614347 · DOI
  44. [58]Ortinski PI Dong J Mungenast A Yue C Takano H Watson DJ. Selective induction of astrocytic gliosis generates deficits in neuronal inhibition. Nat Neurosci. (2010) 13: 584– 91. 10.1038/nn.2535 20418874 PMC3225960 · DOI · Paper page
  45. [59]Woo J Im SK Chun H Jung SY Oh SJ Choi N. Functional characterization of resting and adenovirus-induced reactive astrocytes in three-dimensional culture. Exp Neurobiol. (2017) 26: 158– 67. 10.5607/en.2017.26.3.158 28680301 PMC5491584 · DOI
  46. [63]Sama MA Mathis DM Furman JL Abdul HM Artiushin IA Kraner SD. Interleukin-1beta-dependent signaling between astrocytes and neurons depends critically on astrocytic calcineurin/NFAT activity. J Biol Chem. (2008) 283: 21953– 64. 10.1074/jbc.M800148200 18541537 PMC2494911 · DOI
  47. [64]Abdul HM Sama MA Furman JL Mathis DM Beckett TL Weidner AM. Cognitive decline in Alzheimer's disease is associated with selective changes in calcineurin/NFAT signaling. J Neurosci. (2009) 29: 12957– 69. 10.1523/JNEUROSCI.1064-09.2009 19828810 PMC2782445 · DOI
  48. [65]Hsiao HY Chen YC Chen HM Tu PH Chern Y. A critical role of astrocyte-mediated nuclear factor-kappaB-dependent inflammation in Huntington's disease. Hum Mol Genet. (2013) 22: 1826– 42. 10.1093/hmg/ddt036 23372043 · DOI
  49. [67]Zhang Y Reichel JM Han C Zuniga-Hertz JP Cai D. Astrocytic process plasticity and IKKbeta/NF-kappaB in central control of blood glucose, blood pressure, and body weight. Cell Metab. (2017) 25: 1091– 1102 e1094. 10.1016/j.cmet.2017.04.002 28467927 PMC5576872 · DOI
  50. [68]Xu Z Xiao N Chen Y Huang H Marshall C Gao J. Deletion of aquaporin-4 in APP/PS1 mice exacerbates brain Abeta accumulation and memory deficits. Mol Neurodegener. (2015) 10: 58. 10.1186/s13024-015-0056-1 26526066 PMC4631089 · DOI · Paper page
  51. [69]Asraf K Torika N Apte RN Fleisher-Berkovich S. Microglial activation is modulated by captopril: in vitro and in vivo studies. Front Cell Neurosci. (2018) 12: 116. 10.3389/fncel.2018.00116 29765306 PMC5938337 · DOI
  52. [70]Manocha GD Ghatak A Puig KL Kraner SD Norris CM Combs CK. NFATc2 modulates microglial activation in the abetaPP/PS1 mouse model of alzheimer's disease. J Alzheimers Dis. (2017) 58: 775– 87. 10.3233/JAD-151203 28505967 PMC6265241 · DOI
  53. [71]Sieber MW Jaenisch N Brehm M Guenther M Linnartz-Gerlach B Neumann H. Attenuated inflammatory response in triggering receptor expressed on myeloid cells 2 (TREM2) knock-out mice following stroke. PLoS ONE (2013) 8: e52982. 10.1371/journal.pone.0052982 23301011 PMC3536811 · DOI
  54. [73]Jones BM Bhattacharjee S Dua P Hill JM Zhao Y Lukiw WJ. Regulating amyloidogenesis through the natural triggering receptor expressed in myeloid/microglial cells 2 (TREM2). Front Cell Neurosci. (2014) 8: 94. 10.3389/fncel.2014.00094 24744699 PMC3978349 · DOI
  55. [74]Grienberger C Rochefort NL Adelsberger H Henning HA Hill DN Reichwald J. Staged decline of neuronal function in vivo in an animal model of Alzheimer's disease. Nat Commun. (2012) 3: 774. 10.1038/ncomms1783 22491322 PMC3337977 · DOI
  56. [76]Serrano-Pozo A Mielke ML Muzitansky A Gomez-Isla T Growdon JH Bacskai BJ. Stable size distribution of amyloid plaques over the course of Alzheimer disease. J Neuropathol Exp Neurol. (2012) 71: 694– 701. 10.1097/NEN.0b013e31825e77de 22805771 PMC3407299 · DOI
  57. [77]Hosmane S Yang IH Ruffin A Thakor N Venkatesan A. Circular compartmentalized microfluidic platform: Study of axon-glia interactions. Lab Chip (2010) 10: 741– 7. 10.1039/b918640a 20221562 · DOI
  58. [78]Taylor AM Blurton-Jones M Rhee SW Cribbs DH Cotman CW Jeon NL. A microfluidic culture platform for CNS axonal injury, regeneration and transport. Nat Methods (2005) 2: 599– 605. 10.1038/nmeth777 16094385 PMC1558906 · DOI
  59. [80]Cho H Hashimoto T Wong E Hori Y Wood LB Zhao L. Microfluidic chemotaxis platform for differentiating the roles of soluble and bound amyloid-beta on microglial accumulation. Sci Rep. (2013) 3: 1823. 10.1038/srep01823 23665843 PMC3650586 · DOI
  60. [81]Togo T Akiyama H Iseki E Kondo H Ikeda K Kato M. Occurrence of T cells in the brain of Alzheimer's disease and other neurological diseases. J Neuroimmunol. (2002) 124: 83– 92. 10.1016/S0165-5728(01)00496-9 11958825 · DOI · Paper page
  61. [82]Subramanian S Ayala P Wadsworth TL Harris CJ Vandenbark AA Quinn JF. CCR6: a biomarker for Alzheimer's-like disease in a triple transgenic mouse model. J Alzheimers Dis. (2010) 22: 619– 29. 10.3233/JAD-2010-100852 20847401 PMC2988888 · DOI
  62. [85]Zenaro E Pietronigro E Della Bianca V Piacentino G Marongiu L Budui S. Neutrophils promote Alzheimer's disease-like pathology and cognitive decline via LFA-1 integrin. Nat Med. (2015) 21: 880– 6. 10.1038/nm.3913 26214837 · DOI · Paper page
  63. [86]Park J Wetzel I Baik SH Mook-Jung I Irimia D Cho H The roles of neutrophils in the CNS mediated by reactive microglia in AD. In: Gordon Research Conference: Barriers of the CNS Gordon Research Conference (New London, NH) (2018).
  64. [87]Haenseler W Sansom SN Buchrieser J Newey SE Moore CS Nicholls FJ. A highly efficient human pluripotent stem cell microglia model displays a neuronal-co-culture-specific expression profile and inflammatory response. Stem Cell Rep. (2017) 8: 1727– 42. 10.1016/j.stemcr.2017.05.017 28591653 PMC5470330 · DOI · Paper page
  65. [88]Abud EM Ramirez RN Martinez ES Healy LM Nguyen CHH Newman SA. (2017). iPSC-derived human microglia-like cells to study neurological diseases. Neuron 94: 278– 293 e279. 10.1016/j.neuron.2017.03.042 28426964 PMC5482419 · DOI · Paper page
  66. [91]Jiang T Tan L Zhu XC Zhang QQ Cao L Tan MS. Upregulation of TREM2 ameliorates neuropathology and rescues spatial cognitive impairment in a transgenic mouse model of Alzheimer's disease. Neuropsychopharmacology (2014) 39: 2949– 62. 10.1038/npp.2014.164 25047746 PMC4229581 · DOI · Paper page

Cited by

Sorted by citations

Authors
Chun, H., Marriott, I., Lee, C. J., & Cho, H.
Affiliations
  • Korea Institute of Science and Technology (KR)
  • University of North Carolina at Charlotte (US)
Corresponding author
  • Lee, C. Justin
  • Cho, Hansang
ORCID
Venue
Frontiers in Neurology
Publisher
Frontiers Media SA
Published
2018-09-26
Volume
9
Pages
797-797
ISSN
1664-2295 (ISSN-L)
DOI
10.3389/fneur.2018.00797
PMC
PMC6168676
OpenAlex
W2892858870
Cited by
77
References
25
Citations by year
2026: 3 · 2025: 9 · 2024: 17 · 2023: 7 · 2022: 5 · 2021: 6 · 2020: 23 · 2019: 6
FWCI
0.84
Type
journal article
Language
en
Open access
Licence
Locations
  • Frontiers in Neurology (publishedVersion, cc-by)
  • Europe PMC (PubMed Central) (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Funders
  • Cure Alzheimer's Fund
  • National Research Foundation
  • National Research Foundation of Korea (2018M3C7A1056682)
  • Ministry of Science and ICT, South Korea
Topics
  • Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
  • Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
  • Life Sciences › Neuroscience › Neurology › Neurological Disease Mechanisms and Treatments
Keywords
Alzheimer's disease, glial cells, astrocytes, microglia, neuroinflammation, amyloid plaques, neurofibrillary tangles, tau phosphorylation, neurodegeneration, experimental disease models, oxidative stress, synaptic dysfunction

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