CoChat
Sign Up
Cited by 449Alzheimer's disease research and treatmentsDementia and Cognitive Impairment ResearchNeuroinflammation and Neurodegeneration Mechanisms

Practical considerations for choosing a mouse model of Alzheimer’s disease

Open access
Jankowsky, Joanna L., Zheng, Hui·2017·Molecular Neurodegeneration
DOI 10.1186/s13024-017-0231-7PMC PMC5741956
Open this paper in CoChat — free accountOpen PDF

Abstract

Alzheimer's disease (AD) is behaviorally identified by progressive memory impairment and pathologically characterized by the triad of β-amyloid plaques, neurofibrillary tangles, and neurodegeneration. Genetic mutations and risk factors have been identified that are either causal or modify the disease progression. These genetic and pathological features serve as basis for the creation and validation of mouse models of AD. Efforts made in the past quarter-century have produced over 100 genetically engineered mouse lines that recapitulate some aspects of AD clinicopathology. These models have been valuable resources for understanding genetic interactions that contribute to disease and cellular reactions that are engaged in response. Here we focus on mouse models that have been widely used stalwarts of the field or that are recently developed bellwethers of the future. Rather than providing a summary of each model, we endeavor to compare and contrast the genetic approaches employed and to discuss their respective advantages and limitations. We offer a critical account of the variables which may contribute to inconsistent findings and the factors that should be considered when choosing a model and interpreting the results. We hope to present an insightful review of current AD mouse models and to provide a practical guide for selecting models best matched to the experimental question at hand.

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 · 10.1186/s13024-017-0231-7

Cites

45 of 45 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?

  • These mouse models suffered from potential off-target effects caused by non-physiological overexpression of APP/PSEN1 genes and/or combinations of familial AD mutations, which are not observed in AD patients.

    “they also suffered from potential off-target effects caused by either non-physiological overexpression of APP/PSEN1 genes and/or combinations of familial AD mutations, which are not observed in AD patients [2, 9].”

    From Amyloid-β plaque formation and reactive gliosis are required for induction of cognitive deficits in App knock-in mouse models of Alzheimer’s disease (2019) · cites this paper as [2]

    In “Yin and yang of mouse models” (page unavailable), the paper warns that APP overexpression can produce phenotypes unrelated to Alzheimer’s pathology. “Matching your model to your experimental question” (page unavailable) describes mice combining several familial APP and PSEN1 mutations. The cited passages do not establish that those combinations cause off-target effects or that the combinations are absent in AD patients; they also do not establish the same overexpression concern for PSEN1. (LLM, conf=0.84)

    Experimental — accuracy not yet measured

  • Genetic mutations in ADAD and risk factors for SAD have provided useful information to develop animal AD models, particularly in mice.

    “The genetic mutations found in ADAD and risk factors associated with SAD have provided useful information to develop animal AD models, particularly in mice [150].”

    From Alzheimer's Disease: Treatment Strategies and Their Limitations. (2022) · cites this paper as [150]

  • Transgenic animal models are invaluable tools for studying pathogenic mechanisms and testing therapeutics of AD.

    “transgenic animal models are an invaluable tool for studying pathogenic mechanisms and testing therapeutics of AD (Kitazawa et al., 2012; Jankowsky and Zheng, 2017; Sasaguri et al., 2017).”

    From Age-dependent microstructure alterations in 5xFAD mice by high-resolution diffusion tensor imaging (2022) · cites this paper as Jankowsky and Zheng, 2017

  • Familial AD mutations in APP and PSEN1 genes have been utilized to develop mouse models bearing Aβ pathologies including amyloid plaques and cerebral amyloid angiopathy.

    “Familial AD mutations in APP and PSEN1 genes have been utilized to develop mouse models bearing Aβ pathologies including amyloid plaques and cerebral amyloid angiopathy [2].”

    From Amyloid-β plaque formation and reactive gliosis are required for induction of cognitive deficits in App knock-in mouse models of Alzheimer’s disease (2019) · cites this paper as [2]

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

1 retracted

Flagged first, then by citations

Research works printed but not linked: 197

  1. [1]Goate A Chartier-Harlin MC Mullan M Brown J Crawford F Fidani L Giuffra L Haynes A Irving N James L Segregation of a missense mutation in the amyloid precursor protein gene with familial Alzheimer's disease Nature 1991 349 704 706 10.1038/349704a0 1671712 · DOI · Paper page
  2. [2]Games D Adams D Alessandrini R Barbour R Berthelette P Blackwell C Carr T Clemens J Donaldson T Gillespie F Alzheimer-type neuropathology in transgenic mice overexpressing V717F beta-amyloid precursor protein Nature 1995 373 523 527 10.1038/373523a0 7845465 · DOI · Paper page
  3. [3]Mullan M Crawford F Axelman K Houlden H Lilius L Winblad B Lannfelt L A pathogenic mutation for probable Alzheimer's disease in the APP gene at the N-terminus of beta-amyloid Nat Genet 1992 1 345 347 10.1038/ng0892-345 1302033 · DOI · Paper page
  4. [4]Citron M Oltersdorf T Haass C McConlogue L Hung AY Seubert P Vigo-Pelfrey C Lieberburg I Selkoe DJ Mutation of the beta-amyloid precursor protein in familial Alzheimer's disease increases beta-protein production Nature 1992 360 672 674 10.1038/360672a0 1465129 · DOI · Paper page
  5. [5]Murrell J Farlow M Ghett B Benson MD A mutation in the amyloid precursor protein associated with heridtary Alzheimer's disease Science 1991 254 97 99 10.1126/science.1925564 1925564 · DOI
  6. [6]Eckman CB Mehta ND Crook R Perez-tur J Prihar G Pfeiffer E Graff-Radford N Hinder P Yager D Zenk B A new pathogenic mutation in the APP gene (I716V) increases the relative proportion of a beta 42(43) Hum Mol Genet 1997 6 2087 2089 10.1093/hmg/6.12.2087 9328472 · DOI · Paper page
  7. [7]Guerreiro RJ Baquero M Blesa R Boada M Bras JM Bullido MJ Calado A Crook R Ferreira C Frank A Genetic screening of Alzheimer's disease genes in Iberian and African samples yields novel mutations in presenilins and APP Neurobiol Aging 2010 31 725 731 10.1016/j.neurobiolaging.2008.06.012 18667258 PMC2850052 · DOI
  8. [8]Sherrington R Rogaev EI Liang Y Rogaeva EA Levesque G Ikeda M Chi H Lin C Li G Holman K Cloning of a gene bearing missense mutations in early-onset familial Alzheimer's disease Nature 1995 375 754 760 10.1038/375754a0 7596406 · DOI · Paper page
  9. [9]Alzheimer's Disease Collaborative G The structure of the presenilin 1 (S182) gene and identification of six novel mutations in early onset AD families Nat Genet 1995 11 219 222 10.1038/ng1095-219 7550356 · DOI · Paper page
  10. [10]Moehlmann T Winkler E Xia X Edbauer D Murrell J Capell A Kaether C Zheng H Ghetti B Haass C Steiner H Presenilin-1 mutations of leucine 166 equally affect the generation of the notch and APP intracellular domains independent of their effect on Abeta 42 production Proc Natl Acad Sci U S A 2002 99 8025 8030 10.1073/pnas.112686799 12048239 PMC123014 · DOI
  11. [11]Perez-Tur J Froelich S Prihar G Crook R Baker M Duff K Wragg M Busfield F Lendon C Clark RF A mutation in Alzheimer's disease destroying a splice acceptor site in the presenilin-1 gene Neuroreport 1995 7 297 301 10.1097/00001756-199512000-00071 8742474 · DOI
  12. [12]Van Broeckhoven C Haan J Bakker E Hardy JA Van Hul W Wehnert A Vegter-van der Vlis M Roos RA Amyloid beta protein precursor gene and hereditary cerebral hemorrhage with amyloidosis (Dutch) Science 1990 248 1120 1122 10.1126/science.1971458 1971458 · DOI
  13. [13]Levy E Carman MD Fernandez-Madrid IJ Power MD Lieberburg I van Duinen SG Bots GT Luyendijk W Frangione B Mutation of the Alzheimer's disease amyloid gene in hereditary cerebral hemorrhage, Dutch type Science 1990 248 1124 1126 10.1126/science.2111584 2111584 · DOI
  14. [14]Kamino K Orr HT Payami H Wijsman EM Alonso ME Pulst SM Anderson L O'Dahl S Nemens E White JA Linkage and mutational analysis of familial Alzheimer disease kindreds for the APP gene region Am J Hum Genet 1992 51 998 1014 1415269 PMC1682859
  15. [15]Nilsberth C Westlind-Danielsson A Eckman CB Condron MM Axelman K Forsell C Stenh C Luthman J Teplow DB Younkin SG The 'Arctic' APP mutation (E693G) causes Alzheimer's disease by enhanced Abeta protofibril formation Nat Neurosci 2001 4 887 893 10.1038/nn0901-887 11528419 · DOI · Paper page
  16. [16]Grabowski TJ Cho HS Vonsattel JP Rebeck GW Greenberg SM Novel amyloid precursor protein mutation in an Iowa family with dementia and severe cerebral amyloid angiopathy Ann Neurol 2001 49 697 705 10.1002/ana.1009 11409420 · DOI · Paper page
  17. [17]Cai H Wang Y McCarthy D Wen H Borchelt DR Price DL Wong PC BACE1 is the major beta-secretase for generation of Abeta peptides by neurons Nat Neurosci 2001 4 233 234 10.1038/85064 11224536 · DOI
  18. [18]Xu G Ran Y Fromholt SE Fu C Yachnis AT Golde TE Borchelt DR Murine Abeta over-production produces diffuse and compact Alzheimer-type amyloid deposits Acta Neuropathol Commun 2015 3 72 10.1186/s40478-015-0252-9 26566997 PMC4644287 · DOI · Paper page
  19. [20]Giannakopoulos P Herrmann FR Bussiere T Bouras C Kovari E Perl DP Morrison JH Gold G Hof PR Tangle and neuron numbers, but not amyloid load, predict cognitive status in Alzheimer's disease Neurology 2003 60 1495 1500 10.1212/01.WNL.0000063311.58879.01 12743238 · DOI · Paper page
  20. [21]Mandelkow EM Mandelkow E Biochemistry and cell biology of tau protein in neurofibrillary degeneration Cold Spring Harb. Perspect. Med. 2012 2 a006247 10.1101/cshperspect.a006247 22762014 PMC3385935 · DOI
  21. [23]Braak H Braak E Staging of Alzheimer's disease-related neurofibrillary changes Neurobiol Aging 1995 16 271 278 10.1016/0197-4580(95)00021-6 7566337 · DOI · Paper page
  22. [24]Goedert M Eisenberg DS Crowther RA Propagation of tau aggregates and Neurodegeneration Annu Rev Neurosci 2017 40 189 210 10.1146/annurev-neuro-072116-031153 28772101 · DOI · Paper page
  23. [25]Gendron TF Petrucelli L The role of tau in neurodegeneration Mol Neurodegener 2009 4 13 10.1186/1750-1326-4-13 19284597 PMC2663562 · DOI · Paper page
  24. [26]Hong M Zhukareva V Vogelsberg-Ragaglia V Wszolek Z Reed L Miller BI Geschwind DH Bird TD McKeel D Goate A Mutation-specific functional impairments in distinct tau isoforms of hereditary FTDP-17 Science 1998 282 1914 1917 10.1126/science.282.5395.1914 9836646 · DOI
  25. [28]Ramsden M Kotilinek L Forster C Paulson J McGowan E SantaCruz K Guimaraes A Yue M Lewis J Carlson G Age-dependent neurofibrillary tangle formation, neuron loss, and memory impairment in a mouse model of human tauopathy (P301L) J Neurosci 2005 25 10637 10647 10.1523/JNEUROSCI.3279-05.2005 16291936 PMC6725849 · DOI · Paper page
  26. [29]SantaCruz K Lewis J Spires T Paulson J Kotilinek L Ingelsson M Guimaraes A DeTure M Ramsden M McGowan E Tau suppression in a neurodegenerative mouse model improves memory function Science 2005 309 476 481 10.1126/science.1113694 16020737 PMC1574647 · DOI · Paper page
  27. [30]Yasuda M Johnson-Venkatesh EM Zhang H Parent JM Sutton MA Umemori H Multiple forms of activity-dependent competition refine hippocampal circuits in vivo Neuron 2011 70 1128 1142 10.1016/j.neuron.2011.04.027 21689599 PMC3124368 · DOI
  28. [31]Liu L Drouet V Wu JW Witter MP Small SA Clelland C Duff K Trans-synaptic spread of tau pathology in vivo PLoS One 2012 7 e31302 10.1371/journal.pone.0031302 22312444 PMC3270029 · DOI
  29. [34]Lewis J McGowan E Rockwood J Melrose H Nacharaju P Van Slegtenhorst M Gwinn-Hardy K Paul Murphy M Baker M Yu X Neurofibrillary tangles, amyotrophy and progressive motor disturbance in mice expressing mutant (P301L) tau protein Nat Genet 2000 25 402 405 10.1038/78078 10932182 · DOI · Paper page
  30. [35]Iba M Guo JL McBride JD Zhang B Trojanowski JQ Lee VM Synthetic tau fibrils mediate transmission of neurofibrillary tangles in a transgenic mouse model of Alzheimer's-like tauopathy J Neurosci 2013 33 1024 1037 10.1523/JNEUROSCI.2642-12.2013 23325240 PMC3575082 · DOI · Paper page
  31. [36]Holmes BB Furman JL Mahan TE Yamasaki TR Mirbaha H Eades WC Belaygorod L Cairns NJ Holtzman DM Diamond MI Proteopathic tau seeding predicts tauopathy in vivo Proc Natl Acad Sci U S A 2014 111 E4376 E4385 10.1073/pnas.1411649111 25261551 PMC4205609 · DOI · Paper page
  32. [37]Andorfer C Kress Y Espinoza M de Silva R Tucker KL Barde YA Duff K Davies P Hyperphosphorylation and aggregation of tau in mice expressing normal human tau isoforms J Neurochem 2003 86 582 590 10.1046/j.1471-4159.2003.01879.x 12859672 · DOI · Paper page
  33. [39]Guo Q Li H Cole AL Hur JY Li Y Zheng H Modeling Alzheimer's disease in mouse without mutant protein Overexpression: cooperative and independent effects of Abeta and tau PLoS One 2013 8 e80706 10.1371/journal.pone.0080706 24278307 PMC3835479 · DOI
  34. [40]Yetman MJ Fowler SW Jankowsky JL Humanized tau mice with regionalized Amyloid exhibit behavioral deficits but no pathological interaction PLoS One 2016 11 e0153724 10.1371/journal.pone.0153724 27070146 PMC4829202 · DOI
  35. [44]Bondolfi L Calhoun M Ermini F Kuhn HG Wiederhold KH Walker L Staufenbiel M Jucker M Amyloid-associated neuron loss and gliogenesis in the neocortex of amyloid precursor protein transgenic mice J Neurosci 2002 22 515 522 11784797 PMC6758656
  36. [46]Casas C Sergeant N Itier JM Blanchard V Wirths O van der Kolk N Vingtdeux V van de Steeg E Ret G Canton T Massive CA1/2 neuronal loss with intraneuronal and N-terminal truncated Abeta42 accumulation in a novel Alzheimer transgenic model Am J Pathol 2004 165 1289 1300 10.1016/S0002-9440(10)63388-3 15466394 PMC1618627 · DOI · Paper page
  37. [51]Chishti MA Yang DS Janus C Phinney AL Horne P Pearson J Strome R Zuker N Loukides J French J Early-onset amyloid deposition and cognitive deficits in transgenic mice expressing a double mutant form of amyloid precursor protein 695 J Biol Chem 2001 276 21562 21570 10.1074/jbc.M100710200 11279122 · DOI · Paper page
  38. [53]Westerman MA Cooper-Blacketer D Mariash A Kotilinek L Kawarabayashi T Younkin LH Carlson GA Younkin SG Ashe KH The relationship between Abeta and memory in the Tg2576 mouse model of Alzheimer's disease J Neurosci 2002 22 1858 1867 11880515 PMC6758862
  39. [54]Mucke L Masliah E Yu GQ Mallory M Rockenstein EM Tatsuno G Hu K Kholodenko D Johnson-Wood K McConlogue L High-level neuronal expression of A-beta 1-42 in wild-type human amyloid protein precursor transgenic mice: synaptotoxicity without plaque formation J Neurosci 2000 20 4050 4058 10818140 PMC6772621
  40. [55]Karl T Bhatia S Cheng D Kim WS Garner B Cognitive phenotyping of amyloid precursor protein transgenic J20 mice Behav Brain Res 2012 228 392 397 10.1016/j.bbr.2011.12.021 22197298 · DOI
  41. [56]Webster SJ Bachstetter AD Van Eldik LJ Comprehensive behavioral characterization of an APP/PS-1 double knock-in mouse model of Alzheimer's disease Alzheimers Res Ther 2013 5 28 10.1186/alzrt182 23705774 PMC3706792 · DOI
  42. [57]Li H Guo Q Inoue T Polito VA Tabuchi K Hammer RE Pautler RG Taffet GE Zheng H Vascular and parenchymal amyloid pathology in an Alzheimer disease knock-in mouse model: interplay with cerebral blood flow Mol Neurodegener 2014 9 28 10.1186/1750-1326-9-28 25108425 PMC4132280 · DOI · Paper page
  43. [58]Saito T Matsuba Y Mihira N Takano J Nilsson P Itohara S Iwata N Saido TC Single app knock-in mouse models of Alzheimer's disease Nat Neurosci 2014 17 661 663 10.1038/nn.3697 24728269 · DOI · Paper page
  44. [59]Masuda A Kobayashi Y Kogo N Saito T Saido TC Itohara S Cognitive deficits in single app knock-in mouse models Neurobiol Learn Mem 2016 135 73 82 10.1016/j.nlm.2016.07.001 27377630 · DOI · Paper page
  45. [61]Brunden KR Zhang B Carroll J Yao Y Potuzak JS Hogan AM Iba M James MJ Xie SX Ballatore C Epothilone D improves microtubule density, axonal integrity, and cognition in a transgenic mouse model of tauopathy J Neurosci 2010 30 13861 13866 10.1523/JNEUROSCI.3059-10.2010 20943926 PMC2958430 · DOI · Paper page
  46. [64]Geiszler PC Barron MR Pardon MC Impaired burrowing is the most prominent behavioral deficit of aging htau mice Neuroscience 2016 329 98 111 10.1016/j.neuroscience.2016.05.004 27167086 PMC4915442 · DOI
  47. [65]Morgan D Munireddy S Alamed J DeLeon J Diamond DM Bickford P Hutton M Lewis J McGowan E Gordon MN Apparent behavioral benefits of tau overexpression in P301L tau transgenic mice J. Alzheimers Dis. 2008 15 605 614 10.3233/JAD-2008-15407 19096159 PMC3018352 · DOI
  48. [67]Polito VA Li H Martini-Stoica H Wang B Yang L Xu Y Swartzlander DB Palmieri M di Ronza A Lee VM Selective clearance of aberrant tau proteins and rescue of neurotoxicity by transcription factor EB EMBO Mol. Med. 2014 6 1142 1160 10.15252/emmm.201303671 25069841 PMC4197862 · DOI
  49. [68]Condello C Yuan P Schain A Grutzendler J Microglia constitute a barrier that prevents neurotoxic protofibrillar Abeta42 hotspots around plaques Nat Commun 2015 6 6176 10.1038/ncomms7176 25630253 PMC4311408 · DOI · Paper page
  50. [70]Rodgers SP Born HA Das P Jankowsky JL Transgenic APP expression during postnatal development causes persistent locomotor hyperactivity in the adult Mol Neurodegener 2012 7 28 10.1186/1750-1326-7-28 22709352 PMC3457908 · DOI
  51. [71]Born HA Kim JY Savjani RR Das P Dabaghian YA Guo Q Yoo JW Schuler DR Cirrito JR Zheng H Genetic suppression of transgenic APP rescues hypersynchronous network activity in a mouse model of Alzeimer's disease J Neurosci 2014 34 3826 3840 10.1523/JNEUROSCI.5171-13.2014 24623762 PMC3951689 · DOI · Paper page
  52. [72]van der Kant R Goldstein LS Cellular functions of the amyloid precursor protein from development to dementia Dev Cell 2015 32 502 515 10.1016/j.devcel.2015.01.022 25710536 · DOI
  53. [73]Zheng H Koo EH Biology and pathophysiology of the amyloid precursor protein Mol Neurodegener 2011 6 27 10.1186/1750-1326-6-27 21527012 PMC3098799 · DOI
  54. [74]Dawkins E Small DH Insights into the physiological function of the beta-amyloid precursor protein: beyond Alzheimer's disease J Neurochem 2014 129 756 769 10.1111/jnc.12675 24517464 PMC4314671 · DOI
  55. [75]Muller UC Deller T Korte M Not just amyloid: physiological functions of the amyloid precursor protein family Nat Rev Neurosci 2017 18 281 298 10.1038/nrn.2017.29 28360418 · DOI · Paper page
  56. [76]Sasaguri H Nilsson P Hashimoto S Nagata K Saito T De Strooper B Hardy J Vassar R Winblad B Saido TC APP mouse models for Alzheimer's disease preclinical studies EMBO J 2017 36 2473 2487 28768718 PMC5579350
  57. [77]Nakazono T Lam TN Patel AY Kitazawa M Saito T Saido TC Igarashi KM Impaired in vivo gamma oscillations in the medial Entorhinal cortex of knock-in Alzheimer model Front Syst Neurosci 2017 11 48 10.3389/fnsys.2017.00048 28713250 PMC5491963 · DOI
  58. [78]Malthankar-Phatak G Poplawski S Toraskar N Siman R Combination therapy prevents amyloid-dependent and -independent structural changes Neurobiol Aging 2012 33 1273 1283 10.1016/j.neurobiolaging.2010.12.007 21257234 PMC3094748 · DOI
  59. [79]Zhang C McNeil E Dressler L Siman R Long-lasting impairment in hippocampal neurogenesis associated with amyloid deposition in a knock-in mouse model of familial Alzheimer's disease Exp Neurol 2007 204 77 87 10.1016/j.expneurol.2006.09.018 17070803 PMC1853320 · DOI
  60. [80]Saito T Matsuba Y Yamazaki N Hashimoto S Saido TC Calpain activation in Alzheimer's model mice is an artifact of APP and Presenilin Overexpression J Neurosci 2016 36 9933 9936 10.1523/JNEUROSCI.1907-16.2016 27656030 PMC5030353 · DOI · Paper page
  61. [82]Maphis N Xu G Kokiko-Cochran ON Jiang S Cardona A Ransohoff RM Lamb BT Bhaskar K Reactive microglia drive tau pathology and contribute to the spreading of pathological tau in the brain Brain 2015 138 1738 1755 10.1093/brain/awv081 25833819 PMC4542622 · DOI · Paper page
  62. [83]Ojo JO Mouzon B Greenberg MB Bachmeier C Mullan M Crawford F Repetitive mild traumatic brain injury augments tau pathology and glial activation in aged hTau mice J Neuropathol Exp Neurol 2013 72 137 151 10.1097/NEN.0b013e3182814cdf 23334597 · DOI · Paper page
  63. [84]Alldred MJ Duff KE Ginsberg SD Microarray analysis of CA1 pyramidal neurons in a mouse model of tauopathy reveals progressive synaptic dysfunction Neurobiol Dis 2012 45 751 762 10.1016/j.nbd.2011.10.022 22079237 PMC3259262 · DOI
  64. [85]Dickstein DL Brautigam H Stockton SD Jr Schmeidler J Hof PR Changes in dendritic complexity and spine morphology in transgenic mice expressing human wild-type tau Brain Struct Funct 2010 214 161 179 10.1007/s00429-010-0245-1 20213269 PMC3032082 · DOI
  65. [86]Lamb BT Call LM Slunt HH Bardel KA Lawler AM Eckman CB Younkin SG Holtz G Wagner SL Price DL Altered metabolism of familial Alzheimer's disease-linked amyloid precursor protein variants in yeast artificial chromosome transgenic mice Hum Mol Genet 1997 6 1535 1541 10.1093/hmg/6.9.1535 9285791 · DOI · Paper page
  66. [87]Duff K Knight H Refolo LM Sanders S Yu X Picciano M Malester B Hutton M Adamson J Goedert M Characterization of pathology in transgenic mice over-expressing human genomic and cDNA tau transgenes Neurobiol Dis 2000 7 87 98 10.1006/nbdi.1999.0279 10783293 · DOI
  67. [88]Lamb BT Sisodia SS Lawler AM Slunt HH Kitt CA Kearns WG Pearson PL Price DL Gearhart JD Introduction and expression of the 400 kilobase amyloid precursor protein gene in transgenic mice [corrected] Nat Genet 1993 5 22 30 10.1038/ng0993-22 8220418 · DOI · Paper page
  68. [90]Flood DG Reaume AG Dorfman KS Lin YG Lang DM Trusko SP Savage MJ Annaert WG De Strooper B Siman R Scott RW FAD mutant PS-1 gene-targeted mice: increased a beta 42 and a beta deposition without APP overproduction Neurobiol Aging 2002 23 335 348 10.1016/S0197-4580(01)00330-X 11959395 · DOI · Paper page
  69. [91]Chang EH Savage MJ Flood DG Thomas JM Levy RB Mahadomrongkul V Shirao T Aoki C Huerta PT AMPA receptor downscaling at the onset of Alzheimer's disease pathology in double knockin mice Proc Natl Acad Sci U S A 2006 103 3410 3415 10.1073/pnas.0507313103 16492745 PMC1413872 · DOI · Paper page
  70. [92]Kohler C Ebert U Baumann K Schroder H Alzheimer's disease-like neuropathology of gene-targeted APP-SLxPS1mut mice expressing the amyloid precursor protein at endogenous levels Neurobiol Dis 2005 20 528 540 10.1016/j.nbd.2005.04.009 15921918 · DOI · Paper page
  71. [93]Tsubuki S Takaki Y Saido TC Dutch, Flemish, Italian, and Arctic mutations of APP and resistance of Abeta to physiologically relevant proteolytic degradation Lancet 2003 361 1957 1958 10.1016/S0140-6736(03)13555-6 12801742 · DOI
  72. [94]Sisodia SS Koo EH Hoffman PN Perry G Price DL Identification and transport of full-length amyloid precursor proteins in rat peripheral nervous system J Neurosci 1993 13 3136 3142 8331390 PMC6576678
  73. [95]Hsiao K Chapman P Nilsen S Eckman C Harigaya Y Younkin S Yang F Cole G Correlative memory deficits, Abeta elevation, and amyloid plaques in transgenic mice Science 1996 274 99 102 10.1126/science.274.5284.99 8810256 · DOI · Paper page
  74. [96]Borchelt DR Thinakaran G Eckman CB Lee MK Davenport F Ratovitsky T Prada CM Kim G Seekins S Yager D Familial Alzheimer's disease-linked presenilin 1 variants elevate Abeta1-42/1-40 ratio in vitro and in vivo Neuron 1996 17 1005 1013 10.1016/S0896-6273(00)80230-5 8938131 · DOI · Paper page
  75. [97]Rockenstein EM McConlogue L Tan H Power M Masliah E Mucke L Levels and alternative splicing of amyloid beta protein precursor (APP) transcripts in brains of APP transgenic mice and humans with Alzheimer's disease J Biol Chem 1995 270 28257 28267 10.1074/jbc.270.47.28257 7499323 · DOI
  76. [99]Jankowsky JL Fadale DJ Anderson J Xu GM Gonzales V Jenkins NA Copeland NG Lee MK Younkin LH Wagner SL Mutant presenilins specifically elevate the levels of the 42 residue β-amyloid peptide in vivo: evidence for augmentation of a 42-specific γ-secretase Hum Mol Genet 2004 13 159 170 10.1093/hmg/ddh019 14645205 · DOI · Paper page
  77. [100]Sturchler-Pierrat C Abramowski D Duke M Wiederhold KH Mistl C Rothacher S Ledermann B Burki K Frey P Paganetti PA Two amyloid precursor protein transgenic mouse models with Alzheimer disease-like pathology Proc Natl Acad Sci U S A 1997 94 13287 13292 10.1073/pnas.94.24.13287 9371838 PMC24301 · DOI · Paper page
  78. [102]Lesuisse C Xu G Anderson J Wong M Jankowsky J Holtz G Gonzalez V Wong PC Price DL Tang F Hyper-expression of human apolipoprotein E4 in astroglia and neurons does not enhance amyloid deposition in transgenic mice Hum Mol Genet 2001 10 2525 2537 10.1093/hmg/10.22.2525 11709540 · DOI
  79. [103]Campsall KD Mazerolle CJ De Repentingy Y Kothary R Wallace VA Characterization of transgene expression and Cre recombinase activity in a panel of Thy-1 promoter-Cre transgenic mice Dev. Dyn. 2002 224 135 143 10.1002/dvdy.10092 12112467 · DOI
  80. [104]Borchelt DR Davis J Fischer M Lee MK Slunt HH Ratovitsky T Regard J Copeland NG Jenkins NA Sisodia SS Price DL A vector for expressing foreign genes in the brains and hearts of transgenic mice Genet Anal 1996 13 159 163 10.1016/S1050-3862(96)00167-2 9117892 · DOI
  81. [105]Sasahara M Fries JW Raines EW Gown AM Westrum LE Frosch MP Bonthron DT Ross R Collins T PDGF B-chain in neurons of the central nervous system, posterior pituitary, and in a transgenic model Cell 1991 64 217 227 10.1016/0092-8674(91)90223-L 1986868 · DOI
  82. [106]Davis JA Naruse S Chen H Eckman C Younkin S Price DL Borchelt DR Sisodia SS Wong PC An Alzheimer's disease-linked PS1 variant rescues the developmental abnormalities of PS1-deficient embryos Neuron 1998 20 603 609 10.1016/S0896-6273(00)80998-8 9539132 · DOI
  83. [109]van den Pol AN Ghosh PK Liu RJ Li Y Aghajanian GK Gao XB Hypocretin (orexin) enhances neuron activity and cell synchrony in developing mouse GFP-expressing locus coeruleus J Physiol 2002 541 169 185 10.1113/jphysiol.2002.017426 12015428 PMC2290314 · DOI
  84. [110]Hantman AW van den Pol AN Perl ER Morphological and physiological features of a set of spinal substantia gelatinosa neurons defined by green fluorescent protein expression J Neurosci 2004 24 836 842 10.1523/JNEUROSCI.4221-03.2004 14749428 PMC6729829 · DOI
  85. [111]Setsuie R Wang YL Mochizuki H Osaka H Hayakawa H Ichihara N Li H Furuta A Sano Y Sun YJ Dopaminergic neuronal loss in transgenic mice expressing the Parkinson's disease-associated UCH-L1 I93M mutant Neurochem Int 2007 50 119 129 10.1016/j.neuint.2006.07.015 16965839 · DOI
  86. [112]Feng G Mellor RH Bernstein M Keller-Peck C Nguyen QT Wallace M Nerbonne JM Lichtman JW Sanes JR Imaging neuronal subsets in transgenic mice expressing multiple spectral variants of GFP Neuron 2000 28 41 51 10.1016/S0896-6273(00)00084-2 11086982 · DOI · Paper page
  87. [113]Jankowsky JL Slunt HH Ratovitski T Jenkins NA Copeland NG Borchelt DR Co-expression of multiple transgenes in mouse CNS: a comparison of strategies Biomol Eng 2001 17 157 165 10.1016/S1389-0344(01)00067-3 11337275 · DOI
  88. [114]Carlson GA Borchelt DR Dake A Turner S Danielson V Coffin JD Eckman C Meiners J Nilsen SP Younkin SG Hsiao KK Genetic modification of the phenotypes produced by amyloid precursor protein overexpression in transgenic mice Hum Mol Genet 1997 6 1951 1959 10.1093/hmg/6.11.1951 9302276 · DOI · Paper page
  89. [115]Lehman EJ Kulnane LS Gao Y Petriello MC Pimpis KM Younkin L Dolios G Wang R Younkin SG Lamb BT Genetic background regulates beta-amyloid precursor protein processing and beta-amyloid deposition in the mouse Hum Mol Genet 2003 12 2949 2956 10.1093/hmg/ddg322 14506131 · DOI · Paper page
  90. [116]Jackson HM Onos KD Pepper KW Graham LC Akeson EC Byers C Reinholdt LG Frankel WN Howell GR DBA/2J genetic background exacerbates spontaneous lethal seizures but lessens amyloid deposition in a mouse model of Alzheimer's disease PLoS One 2015 10 e0125897 10.1371/journal.pone.0125897 25933409 PMC4416920 · DOI
  91. [117]Ryman D Gao Y Lamb BT Genetic loci modulating amyloid-beta levels in a mouse model of Alzheimer's disease Neurobiol Aging 2008 29 1190 1198 10.1016/j.neurobiolaging.2007.02.017 17400334 PMC3745768 · DOI
  92. [118]Morihara T Hayashi N Yokokoji M Akatsu H Silverman MA Kimura N Sato M Saito Y Suzuki T Yanagida K Transcriptome analysis of distinct mouse strains reveals kinesin light chain-1 splicing as an amyloid-beta accumulation modifier Proc Natl Acad Sci U S A 2014 111 2638 2643 10.1073/pnas.1307345111 24497505 PMC3932848 · DOI
  93. [119]Borchelt DR Ratovitski T van Lare J Lee MK Gonzales V Jenkins NA Copeland NG Price DL Sisodia SS Accelerated amyloid deposition in the brains of transgenic mice coexpressing mutant presenilin 1 and amyloid precursor proteins Neuron 1997 19 939 945 10.1016/S0896-6273(00)80974-5 9354339 · DOI · Paper page
  94. [121]Gallagher JJ Minogue AM Lynch MA Impaired performance of female APP/PS1 mice in the Morris water maze is coupled with increased Abeta accumulation and microglial activation Neurodegener Dis 2013 11 33 41 10.1159/000337458 22627185 · DOI
  95. [122]Jiao SS Bu XL Liu YH Zhu C Wang QH Shen LL Liu CH Wang YR Yao XQ Wang YJ Sex dimorphism profile of Alzheimer's disease-type pathologies in an APP/PS1 mouse model Neurotox Res 2016 29 256 266 10.1007/s12640-015-9589-x 26707129 · DOI · Paper page
  96. [123]Wang J Tanila H Puolivali J Kadish I van Groen T Gender differences in the amount and deposition of amyloidbeta in APPswe and PS1 double transgenic mice Neurobiol Dis 2003 14 318 327 10.1016/j.nbd.2003.08.009 14678749 · DOI · Paper page
  97. [124]Hirata-Fukae C Li HF Hoe HS Gray AJ Minami SS Hamada K Niikura T Hua F Tsukagoshi-Nagai H Horikoshi-Sakuraba Y Females exhibit more extensive amyloid, but not tau, pathology in an Alzheimer transgenic model Brain Res 2008 1216 92 103 10.1016/j.brainres.2008.03.079 18486110 · DOI · Paper page
  98. [125]Melnikova T Fromholt S Kim H Lee D Xu G Price A Moore BD Golde TE Felsenstein KM Savonenko A Borchelt DR Reversible pathologic and cognitive phenotypes in an inducible model of Alzheimer-amyloidosis J Neurosci 2013 33 3765 3779 10.1523/JNEUROSCI.4251-12.2013 23447589 PMC3711622 · DOI
  99. [126]Schafer S Wirths O Multhaup G Bayer TA Gender dependent APP processing in a transgenic mouse model of Alzheimer's disease J Neural Transm (Vienna) 2007 114 387 394 10.1007/s00702-006-0580-9 17075721 · DOI
  100. [127]Yue M Hanna A Wilson J Roder H Janus C Sex difference in pathology and memory decline in rTg4510 mouse model of tauopathy Neurobiol Aging 2011 32 590 603 10.1016/j.neurobiolaging.2009.04.006 19427061 · DOI
  101. [128]Asuni AA Boutajangout A Quartermain D Sigurdsson EM Immunotherapy targeting pathological tau conformers in a tangle mouse model reduces brain pathology with associated functional improvements J Neurosci 2007 27 9115 9129 10.1523/JNEUROSCI.2361-07.2007 17715348 PMC6672191 · DOI · Paper page
  102. [129]Buccarello L Grignaschi G Castaldo AM Di Giancamillo A Domeneghini C Melcangi RC Borsello T Sex impact on tau-aggregation and postsynaptic protein levels in the P301L mouse model of Tauopathy J. Alzheimers Dis. 2017 56 1279 1292 10.3233/JAD-161087 28157099 · DOI
  103. [130]Clinton LK Billings LM Green KN Caccamo A Ngo J Oddo S McGaugh JL LaFerla FM Age-dependent sexual dimorphism in cognition and stress response in the 3xTg-AD mice Neurobiol Dis 2007 28 76 82 10.1016/j.nbd.2007.06.013 17659878 PMC2756084 · DOI · Paper page
  104. [131]King DL Arendash GW Crawford F Sterk T Menendez J Mullan MJ Progressive and gender-dependent cognitive impairment in the APP(SW) transgenic mouse model for Alzheimer's disease Behav Brain Res 1999 103 145 162 10.1016/S0166-4328(99)00037-6 10513583 · DOI
  105. [132]Granger MW Franko B Taylor MW Messier C George-Hyslop PS Bennett SA A TgCRND8 mouse model of Alzheimer's disease exhibits sexual dimorphisms in behavioral indices of cognitive reserve J. Alzheimers Dis. 2016 51 757 773 10.3233/JAD-150587 26890738 · DOI
  106. [134]Sotiropoulos I Silva J Kimura T Rodrigues AJ Costa P Almeida OF Sousa N Takashima A Female hippocampus vulnerability to environmental stress, a precipitating factor in tau aggregation pathology J. Alzheimers Dis. 2015 43 763 774 25159665
  107. [135]Gimenez-Llort L Arranz L Mate I De la Fuente M Gender-specific neuroimmunoendocrine aging in a triple-transgenic 3xTg-AD mouse model for Alzheimer's disease and its relation with longevity Neuroimmunomodulation 2008 15 331 343 10.1159/000156475 19047809 · DOI · Paper page
  108. [137]Lawlor PA Bland RJ Das P Price RW Holloway V Smithson L Dicker BL During MJ Young D Golde TE Novel rat Alzheimer's disease models based on AAV-mediated gene transfer to selectively increase hippocampal Abeta levels Mol Neurodegener 2007 2 11 10.1186/1750-1326-2-11 17559680 PMC1906777 · DOI · Paper page
  109. [138]Koukouli F Rooy M Maskos U Early and progressive deficit of neuronal activity patterns in a model of local amyloid pathology in mouse prefrontal cortex Aging (Albany NY) 2016 8 3430 3449 10.18632/aging.101136 27999185 PMC5270678 · DOI
  110. [139]Cubinkova V Valachova B Brezovakova V Szabo R Zimova I Kostecka Z Jadhav S Next generation tau models in Alzheimer's disease research - virus based gene delivery systems Acta Virol 2017 61 13 21 10.4149/av_2017_01_13 28105850 · DOI
  111. [140]Caillierez R Begard S Lecolle K Deramecourt V Zommer N Dujardin S Loyens A Dufour N Auregan G Winderickx J Lentiviral delivery of the human wild-type tau protein mediates a slow and progressive neurodegenerative tau pathology in the rat brain Mol. Ther. 2013 21 1358 1368 10.1038/mt.2013.66 23609018 PMC3702115 · DOI
  112. [141]Osinde M Clavaguera F May-Nass R Tolnay M Dev KK Lentivirus tau (P301S) expression in adult amyloid precursor protein (APP)-transgenic mice leads to tangle formation Neuropathol Appl Neurobiol 2008 34 523 531 10.1111/j.1365-2990.2008.00936.x 18282162 · DOI
  113. [142]Klein RL Lin WL Dickson DW Lewis J Hutton M Duff K Meyer EM King MA Rapid neurofibrillary tangle formation after localized gene transfer of mutated tau Am J Pathol 2004 164 347 353 10.1016/S0002-9440(10)63124-0 14695347 PMC1602230 · DOI
  114. [143]Cook C Kang SS Carlomagno Y Lin WL Yue M Kurti A Shinohara M Jansen-West K Perkerson E Castanedes-Casey M Tau deposition drives neuropathological, inflammatory and behavioral abnormalities independently of neuronal loss in a novel mouse model Hum Mol Genet 2015 24 6198 6212 10.1093/hmg/ddv336 26276810 PMC4599677 · DOI · Paper page
  115. [144]Furth PA St Onge L Boger H Gruss P Gossen M Kistner A Bujard H Hennighausen L Temporal control of gene expression in transgenic mice by a tetracycline-responsive promoter Proc Natl Acad Sci U S A 1994 91 9302 9306 10.1073/pnas.91.20.9302 7937760 PMC44800 · DOI
  116. [145]Urlinger S Baron U Thellmann M Hasan MT Bujard H Hillen W Exploring the sequence space for tetracycline-dependent transcriptional activators: novel mutations yield expanded range and sensitivity Proc Natl Acad Sci U S A 2000 97 7963 7968 10.1073/pnas.130192197 10859354 PMC16653 · DOI · Paper page
  117. [146]Mayford M Bach ME Huang YY Wang L Hawkins RD Kandel ER Control of memory formation through regulated expression of a CaMKII transgene Science 1996 274 1678 1683 10.1126/science.274.5293.1678 8939850 · DOI · Paper page
  118. [147]Walker AK Spiller KJ Ge G Zheng A Xu Y Zhou M Tripathy K Kwong LK Trojanowski JQ Lee VM Functional recovery in new mouse models of ALS/FTLD after clearance of pathological cytoplasmic TDP-43 Acta Neuropathol 2015 130 643 660 10.1007/s00401-015-1460-x 26197969 PMC5127391 · DOI
  119. [148]Wang L Sharma K Deng HX Siddique T Grisotti G Liu E Roos RP Restricted expression of mutant SOD1 in spinal motor neurons and interneurons induces motor neuron pathology Neurobiol Dis 2008 29 400 408 10.1016/j.nbd.2007.10.004 18054242 · DOI
  120. [149]Li L Tasic B Micheva KD Ivanov VM Spletter ML Smith SJ Luo L Visualizing the distribution of synapses from individual neurons in the mouse brain PLoS One 2010 5 e11503 10.1371/journal.pone.0011503 20634890 PMC2901335 · DOI
  121. [150]Madisen L Garner AR Shimaoka D Chuong AS Klapoetke NC Li L van der Bourg A Niino Y Egolf L Monetti C Transgenic mice for intersectional targeting of neural sensors and effectors with high specificity and performance Neuron 2015 85 942 958 10.1016/j.neuron.2015.02.022 25741722 PMC4365051 · DOI · Paper page
  122. [151]Hochedlinger K Yamada Y Beard C Jaenisch R Ectopic expression of Oct-4 blocks progenitor-cell differentiation and causes dysplasia in epithelial tissues Cell 2005 121 465 477 10.1016/j.cell.2005.02.018 15882627 · DOI
  123. [152]Premsrirut PK Dow LE Kim SY Camiolo M Malone CD Miething C Scuoppo C Zuber J Dickins RA Kogan SC A rapid and scalable system for studying gene function in mice using conditional RNA interference Cell 2011 145 145 158 10.1016/j.cell.2011.03.012 21458673 PMC3244080 · DOI · Paper page
  124. [153]Yamamoto M Wada N Kitabatake Y Watanabe D Anzai M Yokoyama M Teranishi Y Nakanishi S Reversible suppression of glutamatergic neurotransmission of cerebellar granule cells in vivo by genetically manipulated expression of tetanus neurotoxin light chain J Neurosci 2003 23 6759 6767 12890769 PMC6740723
  125. [154]Tsunemi T Ashe TD Morrison BE Soriano KR Au J Roque RA Lazarowski ER Damian VA Masliah E La Spada AR PGC-1alpha rescues Huntington's disease proteotoxicity by preventing oxidative stress and promoting TFEB function Sci. Transl. Med 2012 4 142ra197 10.1126/scitranslmed.3003799 PMC4096245 22786682 · DOI
  126. [155]Liu P Paulson JB Forster CL Shapiro SL Ashe KH Zahs KR Characterization of a novel mouse model of Alzheimer's disease--Amyloid pathology and unique beta-Amyloid Oligomer profile PLoS One 2015 10 e0126317 10.1371/journal.pone.0126317 25946042 PMC4422728 · DOI
  127. [156]Hoover BR Reed MN Su J Penrod RD Kotilinek LA Grant MK Pitstick R Carlson GA Lanier LM Yuan LL Tau mislocalization to dendritic spines mediates synaptic dysfunction independently of neurodegeneration Neuron 2010 68 1067 1081 10.1016/j.neuron.2010.11.030 21172610 PMC3026458 · DOI · Paper page
  128. [157]Maeda S Djukic B Taneja P Yu GQ Lo I Davis A Craft R Guo W Wang X Kim D Expression of A152T human tau causes age-dependent neuronal dysfunction and loss in transgenic mice EMBO Rep 2016 17 530 551 10.15252/embr.201541438 26931567 PMC4818780 · DOI
  129. [158]Carpenter JW, Marion CJ: Exotic animal formulary. 4th edn. St. Louis, Mo.: Elsevier; 2013.
  130. [159]Golub LM Lee HM Ryan ME Giannobile WV Payne J Sorsa T Tetracyclines inhibit connective tissue breakdown by multiple non-antimicrobial mechanisms Adv Dent Res 1998 12 12 26 10.1177/08959374980120010501 9972117 · DOI
  131. [160]Liu J Xiong W Baca-Regen L Nagase H Baxter BT Mechanism of inhibition of matrix metalloproteinase-2 expression by doxycycline in human aortic smooth muscle cells J Vasc Surg 2003 38 1376 1383 10.1016/S0741-5214(03)01022-X 14681644 · DOI
  132. [161]Golledge J Norman PE Murphy MP Dalman RL Challenges and opportunities in limiting abdominal aortic aneurysm growth J Vasc Surg 2017 65 225 233 10.1016/j.jvs.2016.08.003 27641464 · DOI
  133. [162]Yrjanheikki J Keinanen R Pellikka M Hokfelt T Koistinaho J Tetracyclines inhibit microglial activation and are neuroprotective in global brain ischemia Proc Natl Acad Sci U S A 1998 95 15769 15774 10.1073/pnas.95.26.15769 9861045 PMC28119 · DOI · Paper page
  134. [163]Lazzarini M Martin S Mitkovski M Vozari RR Stuhmer W Bel ED Doxycycline restrains glia and confers neuroprotection in a 6-OHDA Parkinson model Glia 2013 61 1084 1100 10.1002/glia.22496 23595698 · DOI
  135. [164]Cho Y Son HJ Kim EM Choi JH Kim ST Ji IJ Choi DH Joh TH Kim YS Hwang O Doxycycline is neuroprotective against nigral dopaminergic degeneration by a dual mechanism involving MMP-3 Neurotox Res 2009 16 361 371 10.1007/s12640-009-9078-1 19582534 · DOI · Paper page
  136. [165]Zhang GB Feng YH Wang PQ Song JH Wang P Wang SA A study on the protective role of doxycycline upon dopaminergic neuron of LPS-PD rat model rat Eur Rev Med Pharmacol Sci 2015 19 3468 3474 26439044
  137. [166]Maezawa I Zimin PI Wulff H Jin LW Amyloid-beta protein oligomer at low nanomolar concentrations activates microglia and induces microglial neurotoxicity J Biol Chem 2011 286 3693 3706 10.1074/jbc.M110.135244 20971854 PMC3030372 · DOI
  138. [167]Lai AY Todd KG Hypoxia-activated microglial mediators of neuronal survival are differentially regulated by tetracyclines Glia 2006 53 809 816 10.1002/glia.20335 16541436 · DOI
  139. [168]Karlsson M Hammers S Nilsson-Ehle I Malmborg AS Wretlind B Concentrations of doxycycline and penicillin G in sera and cerebrospinal fluid of patients treated for neuroborreliosis Antimicrob Agents Chemother 1996 40 1104 1107 8723448 PMC163273
  140. [169]Maier K Merkler D Gerber J Taheri N Kuhnert AV Williams SK Neusch C Bahr M Diem R Multiple neuroprotective mechanisms of minocycline in autoimmune CNS inflammation Neurobiol Dis 2007 25 514 525 10.1016/j.nbd.2006.10.022 17239606 · DOI
  141. [170]Peng J Xie L Stevenson FF Melov S Di Monte DA Andersen JK Nigrostriatal dopaminergic neurodegeneration in the weaver mouse is mediated via neuroinflammation and alleviated by minocycline administration J Neurosci 2006 26 11644 11651 10.1523/JNEUROSCI.3447-06.2006 17093086 PMC6674792 · DOI · Paper page
  142. [171]Fan LW Lin S Pang Y Rhodes PG Cai Z Minocycline attenuates hypoxia-ischemia-induced neurological dysfunction and brain injury in the juvenile rat Eur J Neurosci 2006 24 341 350 10.1111/j.1460-9568.2006.04918.x 16836639 · DOI
  143. [172]Hunter CL Bachman D Granholm AC Minocycline prevents cholinergic loss in a mouse model of Down's syndrome Ann Neurol 2004 56 675 688 10.1002/ana.20250 15468085 · DOI
  144. [173]Garwood CJ Cooper JD Hanger DP Noble W Anti-inflammatory impact of minocycline in a mouse model of tauopathy Front Psychiatry 2010 1 136 10.3389/fpsyt.2010.00136 21423446 PMC3059645 · DOI · Paper page
  145. [174]Hou Y Ryu CH Park KY Kim SM Jeong CH Jeun SS Effective combination of human bone marrow mesenchymal stem cells and minocycline in experimental autoimmune encephalomyelitis mice Stem Cell Res Ther 2013 4 77 10.1186/scrt228 23826999 PMC3854709 · DOI
  146. [175]Aras M Urfali B Serarslan Y Ozgur T Ulutas KT Urfali S Altas M Yilmaz N Protective effects of minocycline against short-term ischemia-reperfusion injury in rat brain Pediatr Neurosurg 2013 49 172 178 10.1159/000362202 24801142 · DOI
  147. [176]Chen M Ona VO Li M Ferrante RJ Fink KB Zhu S Bian J Guo L Farrell LA Hersch SM Minocycline inhibits caspase-1 and caspase-3 expression and delays mortality in a transgenic mouse model of Huntington disease Nat Med 2000 6 797 801 10.1038/80538 10888929 · DOI
  148. [177]Yrjanheikki J Tikka T Keinanen R Goldsteins G Chan PH Koistinaho J A tetracycline derivative, minocycline, reduces inflammation and protects against focal cerebral ischemia with a wide therapeutic window Proc Natl Acad Sci U S A 1999 96 13496 13500 10.1073/pnas.96.23.13496 10557349 PMC23976 · DOI
  149. [178]Fowler SW Chiang AC Savjani RR Larson ME Sherman MA Schuler DR Cirrito JR Lesne SE Jankowsky JL Genetic modulation of soluble abeta rescues cognitive and synaptic impairment in a mouse model of Alzheimer's disease J Neurosci 2014 34 7871 7885 10.1523/JNEUROSCI.0572-14.2014 24899710 PMC4044248 · DOI
  150. [179]Igaz LM Kwong LK Lee EB Chen-Plotkin A Swanson E Unger T Malunda J Xu Y Winton MJ Trojanowski JQ Lee VM Dysregulation of the ALS-associated gene TDP-43 leads to neuronal death and degeneration in mice J Clin Invest 2011 121 726 738 10.1172/JCI44867 21206091 PMC3026736 · DOI
  151. [180]Bejar R Yasuda R Krugers H Hood K Mayford M Transgenic calmodulin-dependent protein kinase II activation: dose-dependent effects on synaptic plasticity, learning, and memory J Neurosci 2002 22 5719 5726 12097524 PMC6758231
  152. [181]Glazewski S Bejar R Mayford M Fox K The effect of autonomous alpha-CaMKII expression on sensory responses and experience-dependent plasticity in mouse barrel cortex Neuropharmacology 2001 41 771 778 10.1016/S0028-3908(01)00097-1 11640932 · DOI
  153. [184]McCloskey DT Turnbull L Swigart PM Zambon AC Turcato S Joho S Grossman W Conklin BR Simpson PC Baker AJ Cardiac transgenesis with the tetracycline transactivator changes myocardial function and gene expression Physiol Genomics 2005 22 118 126 10.1152/physiolgenomics.00016.2005 15797971 · DOI · Paper page
  154. [186]Sisson TH Hansen JM Shah M Hanson KE Du M Ling T Simon RH Christensen PJ Expression of the reverse tetracycline-transactivator gene causes emphysema-like changes in mice Am J Respir Cell Mol Biol 2006 34 552 560 10.1165/rcmb.2005-0378OC 16415250 PMC2644220 · DOI · Paper page
  155. [187]Strittmatter WJ Saunders AM Schmechel D Pericak-Vance M Enghild J Salvesen GS Roses AD Apolipoprotein E: high-avidity binding to beta-amyloid and increased frequency of type 4 allele in late-onset familial Alzheimer disease Proc Natl Acad Sci U S A 1993 90 1977 1981 10.1073/pnas.90.5.1977 8446617 PMC46003 · DOI · Paper page
  156. [188]Karch CM Goate AM Alzheimer's disease risk genes and mechanisms of disease pathogenesis Biol Psychiatry 2015 77 43 51 10.1016/j.biopsych.2014.05.006 24951455 PMC4234692 · DOI · Paper page
  157. [189]Efthymiou AG Goate AM Late onset Alzheimer's disease genetics implicates microglial pathways in disease risk Mol Neurodegener 2017 12 43 10.1186/s13024-017-0184-x 28549481 PMC5446752 · DOI · Paper page
  158. [190]Guerreiro R Wojtas A Bras J Carrasquillo M Rogaeva E Majounie E Cruchaga C Sassi C Kauwe JS Younkin S TREM2 variants in Alzheimer's disease N Engl J Med 2013 368 117 127 10.1056/NEJMoa1211851 23150934 PMC3631573 · DOI · Paper page
  159. [191]Jonsson T Stefansson H Steinberg S Jonsdottir I Jonsson PV Snaedal J Bjornsson S Huttenlocher J Levey AI Lah JJ Variant of TREM2 associated with the risk of Alzheimer's disease N Engl J Med 2013 368 107 116 10.1056/NEJMoa1211103 23150908 PMC3677583 · DOI · Paper page
  160. [192]Chen HK Liu Z Meyer-Franke A Brodbeck J Miranda RD McGuire JG Pleiss MA Ji ZS Balestra ME Walker DW Small molecule structure correctors abolish detrimental effects of apolipoprotein E4 in cultured neurons J Biol Chem 2012 287 5253 5266 10.1074/jbc.M111.276162 22158868 PMC3285306 · DOI · Paper page
  161. [193]Piedrahita JA Zhang SH Hagaman JR Oliver PM Maeda N Generation of mice carrying a mutant apolipoprotein E gene inactivated by gene targeting in embryonic stem cells Proc Natl Acad Sci U S A 1992 89 4471 4475 10.1073/pnas.89.10.4471 1584779 PMC49104 · DOI · Paper page
  162. [194]Zhang SH Reddick RL Piedrahita JA Maeda N Spontaneous hypercholesterolemia and arterial lesions in mice lacking apolipoprotein E Science 1992 258 468 471 10.1126/science.1411543 1411543 · DOI · Paper page
  163. [195]Yang CP Gilley JA Zhang G Kernie SG ApoE is required for maintenance of the dentate gyrus neural progenitor pool Development 2011 138 4351 4362 10.1242/dev.065540 21880781 PMC3177307 · DOI · Paper page
  164. [197]Mann KM Thorngate FE Katoh-Fukui Y Hamanaka H Williams DL Fujita S Lamb BT Independent effects of APOE on cholesterol metabolism and brain Abeta levels in an Alzheimer disease mouse model Hum Mol Genet 2004 13 1959 1968 10.1093/hmg/ddh199 15229191 · DOI · Paper page
  165. [200]Knouff C Hinsdale ME Mezdour H Altenburg MK Watanabe M Quarfordt SH Sullivan PM Maeda N Apo E structure determines VLDL clearance and atherosclerosis risk in mice J Clin Invest 1999 103 1579 1586 10.1172/JCI6172 10359567 PMC408371 · DOI · Paper page
  166. [201]Shi Y Yamada K Liddelow SA Smith ST Zhao L Luo W Tsai RM Spina S Grinberg LT Rojas JC ApoE4 markedly exacerbates tau-mediated neurodegeneration in a mouse model of tauopathy Nature 2017 549 523 527 10.1038/nature24016 28959956 PMC5641217 · DOI · Paper page
  167. [202]Brendza RP Bales KR Paul SM Holtzman DM Role of apoE/Abeta interactions in Alzheimer's disease: insights from transgenic mouse models Mol Psychiatry 2002 7 132 135 10.1038/sj.mp.4001006 11840304 · DOI
  168. [203]Liu CC Liu CC Kanekiyo T Xu H Bu G Apolipoprotein E and Alzheimer disease: risk, mechanisms and therapy Nat Rev Neurol 2013 9 106 118 10.1038/nrneurol.2012.263 23296339 PMC3726719 · DOI · Paper page
  169. [205]Turnbull IR Gilfillan S Cella M Aoshi T Miller M Piccio L Hernandez M Colonna M Cutting edge: TREM-2 attenuates macrophage activation J Immunol 2006 177 3520 3524 10.4049/jimmunol.177.6.3520 16951310 · DOI · Paper page
  170. [208]Kleinberger G Brendel M Mracsko E Wefers B Groeneweg L Xiang X Focke C Deussing M Suarez-Calvet M Mazaheri F The FTD-like syndrome causing TREM2 T66M mutation impairs microglia function, brain perfusion, and glucose metabolism EMBO J 2017 36 1837 1853 10.15252/embj.201796516 28559417 PMC5494459 · DOI
  171. [209]Niwa H Yamamura K Miyazaki J Efficient selection for high-expression transfectants with a novel eukaryotic vector Gene. 1991 108 193 9 10.1016/0378-1119(91)90434-D 1660837 · DOI
  172. [210]Davis J Xu F Deane R Romanov G Previti ML Zeigler K Zlokovic BV Van Nostrand WE Early-onset and robust cerebral microvascular accumulation of amyloid beta-protein in transgenic mice expressing low levels of a vasculotropic Dutch/Iowa mutant form of amyloid beta-protein precursor J Biol Chem 2004 279 20296 20306 10.1074/jbc.M312946200 14985348 · DOI · Paper page
  173. [211]Radde R Bolmont T Kaeser SA Coomaraswamy J Lindau D Stoltze L Calhoun ME Jaggi F Wolburg H Gengler S Abeta42-driven cerebral amyloidosis in transgenic mice reveals early and robust pathology EMBO Rep 2006 7 940 946 10.1038/sj.embor.7400784 16906128 PMC1559665 · DOI · Paper page
  174. [212]Ishihara T Hong M Zhang B Nakagawa Y Lee MK Trojanowski JQ Lee VM Age-dependent emergence and progression of a tauopathy in transgenic mice overexpressing the shortest human tau isoform Neuron 1999 24 751 762 10.1016/S0896-6273(00)81127-7 10595524 · DOI · Paper page
  175. [213]Allen B Ingram E Takao M Smith MJ Jakes R Virdee K Yoshida H Holzer M Craxton M Emson PC Abundant tau filaments and nonapoptotic neurodegeneration in transgenic mice expressing human P301S tau protein J Neurosci 2002 22 9340 9351 12417659 PMC6758022
  176. [214]Guo Q Fu W Sopher BL Miller MW Ware CB Martin GM Mattson MP Increased vulnerability of hippocampal neurons to excitotoxic necrosis in presenilin-1 mutant knock-in mice Nat Med 1999 5 101 106 10.1038/4789 9883847 · DOI · Paper page
  177. [216]Ubhi K Rockenstein E Doppler E Mante M Adame A Patrick C Trejo M Crews L Paulino A Moessler H Masliah E Neurofibrillary and neurodegenerative pathology in APP-transgenic mice injected with AAV2-mutant TAU: neuroprotective effects of Cerebrolysin Acta Neuropathol 2009 117 699 712 10.1007/s00401-009-0505-4 19252918 PMC3049872 · DOI
  178. [217]Jaworski T Dewachter I Lechat B Croes S Termont A Demedts D Borghgraef P Devijver H Filipkowski RK Kaczmarek L AAV-tau mediates pyramidal neurodegeneration by cell-cycle re-entry without neurofibrillary tangle formation in wild-type mice PLoS One 2009 4 e7280 10.1371/journal.pone.0007280 19794916 PMC2748684 · DOI
  179. [218]Siman R Lin YG Malthankar-Phatak G Dong Y A rapid gene delivery-based mouse model for early-stage Alzheimer disease-type tauopathy J Neuropathol Exp Neurol 2013 72 1062 1071 10.1097/NEN.0000000000000006 24128676 PMC3815088 · DOI
  180. [220]Platt TL Beckett TL Kohler K Niedowicz DM Murphy MP Obesity, diabetes, and leptin resistance promote tau pathology in a mouse model of disease Neuroscience 2016 315 162 174 10.1016/j.neuroscience.2015.12.011 26701291 PMC4715963 · DOI
  181. [221]Maeda N Johnson L Kim S Hagaman J Friedman M Reddick R Anatomical differences and atherosclerosis in apolipoprotein E-deficient mice with 129/SvEv and C57BL/6 genetic backgrounds Atherosclerosis 2007 195 75 82 10.1016/j.atherosclerosis.2006.12.006 17275002 PMC2151972 · DOI
  182. [222]Bero AW Yan P Roh JH Cirrito JR Stewart FR Raichle ME Lee JM Holtzman DM Neuronal activity regulates the regional vulnerability to amyloid-beta deposition Nat Neurosci 2011 14 750 756 10.1038/nn.2801 21532579 PMC3102784 · DOI · Paper page
  183. [223]Sevigny J Chiao P Bussiere T Weinreb PH Williams L Maier M Dunstan R Salloway S Chen T Ling Y The antibody aducanumab reduces Abeta plaques in Alzheimer's disease Nature 2016 537 50 56 10.1038/nature19323 27582220 · DOI · Paper page
  184. [224]Amar F, Sherman MA, Rush T, Larson M, Boyle G, Chang L, Gotz J, Buisson A, Lesne SE. The amyloid-beta oligomer Abeta*56 induces specific alterations in neuronal signaling that lead to tau phosphorylation and aggregation. Sci Signal. 2017;10 PMC5859319 28487416
  185. [225]Liu CC Zhao N Yamaguchi Y Cirrito JR Kanekiyo T Holtzman DM Bu G Neuronal heparan sulfates promote amyloid pathology by modulating brain amyloid-beta clearance and aggregation in Alzheimer's disease Sci. Transl. Med 2016 8 332ra344 PMC5512541 27030596
  186. [226]Ofengeim D Mazzitelli S Ito Y DeWitt JP Mifflin L Zou C Das S Adiconis X Chen H Zhu H RIPK1 mediates a disease-associated microglial response in Alzheimer's disease Proc Natl Acad Sci U S A 2017 114 E8788 E8797 10.1073/pnas.1701330114 28904096 PMC5642727 · DOI
  187. [227]Wojtas AM Kang SS Olley BM Gatherer M Shinohara M Lozano PA Liu CC Kurti A Baker KE Dickson DW Loss of clusterin shifts amyloid deposition to the cerebrovasculature via disruption of perivascular drainage pathways Proc Natl Acad Sci U S A 2017 114 E6962 E6971 10.1073/pnas.1701137114 28701379 PMC5565413 · DOI
  188. [230]Andrew RJ Fernandez CG Stanley M Jiang H Nguyen P Rice RC Buggia-Prevot V De Rossi P Vetrivel KS Lamb R Lack of BACE1 S-palmitoylation reduces amyloid burden and mitigates memory deficits in transgenic mouse models of Alzheimer's disease Proc Natl Acad Sci U S A 2017 114 E9665 E9674 10.1073/pnas.1708568114 29078331 PMC5692556 · DOI
  189. [231]Caccamo A Branca C Talboom JS Shaw DM Turner D Ma L Messina A Huang Z Wu J Oddo S Reducing ribosomal protein S6 Kinase 1 expression improves spatial memory and synaptic plasticity in a mouse model of Alzheimer's disease J Neurosci 2015 35 14042 14056 10.1523/JNEUROSCI.2781-15.2015 26468204 PMC4604237 · DOI
  190. [232]Mably AJ Gereke BJ Jones DT Colgin LL Impairments in spatial representations and rhythmic coordination of place cells in the 3xTg mouse model of Alzheimer's disease Hippocampus 2017 27 378 392 10.1002/hipo.22697 28032686 · DOI
  191. [233]Zenaro E Pietronigro E Della Bianca V Piacentino G Marongiu L Budui S Turano E Rossi B Angiari S Dusi S Neutrophils promote Alzheimer's disease-like pathology and cognitive decline via LFA-1 integrin Nat Med 2015 21 880 886 10.1038/nm.3913 26214837 · DOI · Paper page
  192. [234]Sherman MA LaCroix M Amar F Larson ME Forster C Aguzzi A Bennett DA Ramsden M Lesne SE Soluble conformers of Abeta and tau Alter selective proteins governing axonal transport J Neurosci 2016 36 9647 9658 10.1523/JNEUROSCI.1899-16.2016 27629715 PMC5039246 · DOI
  193. [235]Cheng J Ji D Rigid firing sequences undermine spatial memory codes in a neurodegenerative mouse model elife 2013 2 e00647 10.7554/eLife.00647 23805379 PMC3691575 · DOI
  194. [237]Kaufman SK Sanders DW Thomas TL Ruchinskas AJ Vaquer-Alicea J Sharma AM Miller TM Diamond MI Tau Prion strains dictate patterns of cell pathology, progression rate, and regional vulnerability in vivo Neuron 2016 92 796 812 10.1016/j.neuron.2016.09.055 27974162 PMC5392364 · DOI · Paper page
  195. [238]Boluda S Iba M Zhang B Raible KM Lee VM Trojanowski JQ Differential induction and spread of tau pathology in young PS19 tau transgenic mice following intracerebral injections of pathological tau from Alzheimer's disease or corticobasal degeneration brains Acta Neuropathol 2015 129 221 237 10.1007/s00401-014-1373-0 25534024 PMC4305460 · DOI
  196. [239]Zhang H Wu L Pchitskaya E Zakharova O Saito T Saido T Bezprozvanny I Neuronal store-operated calcium entry and mushroom spine loss in Amyloid precursor protein knock-in mouse model of Alzheimer's disease J Neurosci 2015 35 13275 13286 10.1523/JNEUROSCI.1034-15.2015 26424877 PMC4588605 · DOI
  197. [240]Hernandez AL, Shah D, Craessaerts K, Saido T, Saito T, De Strooper B, Van der Linden A, D'Hooge R. Subtle behavioral changes and increased prefrontal-hippocampal network synchronicity in APP(NL-G-F) mice before prominent plaque deposition. Behav Brain Res. 2017; 29158112

Cited by

Sorted by citations

Authors
Jankowsky, J. L., & Zheng, H.
Affiliations
Baylor College of Medicine (US)
Corresponding author
  • Jankowsky, Joanna L.
  • Zheng, Hui
ORCID
Venue
Molecular Neurodegeneration
Publisher
Springer Science and Business Media LLC
Published
2017-12
Volume
12
Issue
1
Pages
89-89
ISSN
1750-1326 (ISSN-L)
DOI
10.1186/s13024-017-0231-7
PMC
PMC5741956
OpenAlex
W2779463443
Cited by
449
References
45
Citations by year
2026: 35 · 2025: 42 · 2024: 67 · 2023: 56 · 2022: 70 · 2021: 68 · 2020: 49 · 2019: 39 · 2018: 23
FWCI
3.73
Type
journal article
Language
en
Open access
Licence
Locations
  • Molecular Neurodegeneration (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
  • National Institute on Aging (AG058188, AG056028, AG054160, AG020670, AG032051, AG054111)
  • National Institute of Neurological Disorders and Stroke (NS092615, NS093652)
Topics
  • Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
  • Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
  • Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
Keywords
Alzheimer's disease, mouse model, amyloid plaques, neurofibrillary tangles, neurodegeneration, memory impairment, genetic mutations, model selection, genetic interactions, reproducibility of findings
MeSH terms
Alzheimer Disease, Animals, Disease Models, Animal, Humans, Mice, Transgenic, Amyloid beta-Protein Precursor, Cerebral Amyloid Angiopathy, Neurofibrillary Tangles, Mice, Knockout, Neurodegenerative Diseases, Mice, Plaque, Amyloid, Cognitive 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