Cited by 23

APOE4 Promotes Tonic-Clonic Seizures, an Effect Modified by Familial Alzheimer’s Disease Mutations

Lamoureux, Lorissa, Marottoli, Felecia M., Tseng, Kuei Y., Tai, Leon M.·2021·Frontiers in Cell and Developmental Biology

Abstract

Seizures are emerging as a common symptom in Alzheimer’s disease (AD) patients, often attributed to high levels of amyloid β (Aβ). However, the extent that AD disease risk factors modulate seizure activity in aging and AD-relevant contexts is unclear. APOE4 is the greatest genetic risk factor for AD and has been linked to seizures independent of AD and Aβ. The goal of the present study was to evaluate the role of APOE genotype in modulating seizures in the absence and presence of high Aβ levels in vivo . To achieve this goal, we utilized EFAD mice, which express human APOE3 or APOE4 in the absence (EFAD−) or presence (EFAD+) of familial AD mutations that result in Aβ overproduction. When quantified during cage change day, we found that unlike APOE3 , APOE4 is associated with tonic-clonic seizures. Interestingly, there were lower tonic-clonic seizures in E4FAD+ mice compared to E4FAD− mice. Restraint handing and auditory stimuli failed to recapitulate the tonic-clonic phenotype in EFAD mice that express APOE4 . However, after chemical-induction with pentylenetetrazole, there was a higher incidence of tonic-clonic seizures with APOE4 compared to APOE3 . Interestingly, the distribution of seizures to the tonic-clonic phenotype was higher with FAD mutations. These data support that APOE4 is associated with higher tonic-clonic seizures in vivo , and that FAD mutations impact tonic-clonic seizures in a paradigm dependent manner.

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/fcell.2021.656521

Cites

5 of 5 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: 75

  1. Abe Y. Ikegawa N. Yoshida K. Muramatsu K. Hattori S. Kawai K. (2020). Behavioral and electrophysiological evidence for a neuroprotective role of aquaporin-4 in the 5xFAD transgenic mice model. Acta Neuropathol. Commun. 8: 67. 10.1186/s40478-020-00936-3 32398151 PMC7218576 · DOI
  2. Amatniek J. C. Hauser W. A. DelCastillo-Castaneda C. Jacobs D. M. Marder K. Bell K. (2006). Incidence and predictors of seizures in patients with Alzheimer’s disease. Epilepsia 47 867– 872. 10.1111/j.1528-1167.2006.00554.x 16686651 · DOI
  3. Angel A. Volkman R. Royal T. G. Offen D. (2020). Caspase-6 knockout in the 5xFAD model of Alzheimer’s disease reveals favorable outcome on memory and neurological hallmarks. Int. J. Mol. Sci. 21: 1144. 10.3390/ijms21031144 32050445 PMC7037950 · DOI
  4. Balu D. Karstens A. J. Loukenas E. Maldonado Weng J. York J. M. Valencia-Olvera A. C. (2019). The role of APOE in transgenic mouse models of AD. Neurosci. Lett. 707: 134285. 10.1016/j.neulet.2019.134285 31150730 PMC6717006 · DOI · Paper page
  5. Bernardi S. Scaldaferri N. Vanacore N. Trebbastoni A. Francia A. D’Amico A. (2010). Seizures in Alzheimer’s disease: a retrospective study of a cohort of outpatients. Epileptic Disord. 12 16– 21. 10.1684/epd.2010.0290 20172846 · DOI
  6. Bezzina C. Verret L. Juan C. Remaud J. Halley H. Rampon C. (2015). Early onset of hypersynchronous network activity and expression of a marker of chronic seizures in the Tg2576 mouse model of Alzheimer’s disease. PLoS One 10: e0119910. 10.1371/journal.pone.0119910 25768013 PMC4358928 · DOI
  7. Bour A. Grootendorst J. Vogel E. Kelche C. Dodart J. C. Bales K. (2008). Middle-aged human apoE4 targeted-replacement mice show retention deficits on a wide range of spatial memory tasks. Behav. Brain Res. 193 174– 182. 10.1016/j.bbr.2008.05.008 18572260 · DOI · Paper page
  8. Brault V. Martin B. Costet N. Bizot J. C. Herault Y. (2011). Characterization of PTZ-induced seizure susceptibility in a down syndrome mouse model that overexpresses CSTB. PLoS One 6: e27845. 10.1371/journal.pone.0027845 22140471 PMC3227573 · DOI
  9. Briellmann R. S. Torn-Broers Y. Busuttil B. E. Major B. J. Kalnins R. M. Olsen M. (2000). APOE epsilon4 genotype is associated with an earlier onset of chronic temporal lobe epilepsy. Neurology 55 435– 437. 10.1212/wnl.55.3.435 10932283 · DOI
  10. Brunetti V. D’Atri A. Della Marca G. Vollono C. Marra C. Vita M. G. (2020). Subclinical epileptiform activity during sleep in Alzheimer’s disease and mild cognitive impairment. Clin. Neurophysiol. 131 1011– 1018. 10.1016/j.clinph.2020.02.015 32193162 · DOI
  11. Busch R. M. Lineweaver T. T. Naugle R. I. Kim K. H. Gong Y. Tilelli C. Q. (2007). ApoE-epsilon4 is associated with reduced memory in long-standing intractable temporal lobe epilepsy. Neurology 68 409– 414. 10.1212/01.wnl.0000253021.60887.db 17283313 · DOI
  12. Cheng C. H. Liu C. J. Ou S. M. Yeh C. M. Chen T. J. Lin Y. Y. (2015). Incidence and risk of seizures in Alzheimer’s disease: a nationwide population-based cohort study. Epilepsy Res. 115 63– 66. 10.1016/j.eplepsyres.2015.05.009 26220378 · DOI
  13. Costa C. Romoli M. Liguori C. Farotti L. Eusebi P. Bedetti C. (2019). Alzheimer’s disease and late-onset epilepsy of unknown origin: two faces of beta amyloid pathology. Neurobiol. Aging 73 61– 67. 10.1016/j.neurobiolaging.2018.09.006 30317034 · DOI
  14. Cretin B. Sellal F. Philippi N. Bousiges O. Di Bitonto L. Martin-Hunyadi C. (2016). Epileptic prodromal Alzheimer’s disease, a retrospective study of 13 new cases: expanding the spectrum of Alzheimer’s disease to an epileptic variant? J. Alzheimers Dis. 52 1125– 1133. 10.3233/JAD-150096 27104892 · DOI
  15. Del Vecchio R. A. Gold L. H. Novick S. J. Wong G. Hyde L. A. (2004). Increased seizure threshold and severity in young transgenic CRND8 mice. Neurosci. Lett. 367 164– 167. 10.1016/j.neulet.2004.05.107 15331144 · DOI
  16. Diaz-Arrastia R. Gong Y. Fair S. Scott K. D. Garcia M. C. Carlile M. C. (2003). Increased risk of late posttraumatic seizures associated with inheritance of APOE epsilon4 allele. Arch. Neurol. 60 818– 822. 10.1001/archneur.60.6.818 12810485 · DOI
  17. Dickerson B. C. Salat D. H. Greve D. N. Chua E. F. Rand-Giovannetti E. Rentz D. M. (2005). Increased hippocampal activation in mild cognitive impairment compared to normal aging and AD. Neurology 65 404– 411. 10.1212/01.wnl.0000171450.97464.49 16087905 PMC4335677 · DOI · Paper page
  18. DiFrancesco J. C. Tremolizzo L. Polonia V. Giussani G. Bianchi E. Franchi C. (2017). Adult-onset epilepsy in presymptomatic Alzheimer’s disease: a retrospective study. J. Alzheimers Dis. 60 1267– 1274. 10.3233/JAD-170392 28968234 · DOI
  19. Duke J. L. Zammit T. G. Lawson D. M. (2001). The effects of routine cage-changing on cardiovascular and behavioral parameters in male sprague-dawley rats. Contemp. Top. Lab. Anim. Sci. 40 17– 20. 11300670
  20. Flowers S. A. Rebeck G. W. (2020). APOE in the normal brain. Neurobiol. Dis. 136: 104724. 10.1016/j.nbd.2019.104724 31911114 PMC7002287 · DOI · Paper page
  21. Gambardella A. Aguglia U. Chifari R. Labate A. Manna I. Serra P. (2005). ApoE epsilon4 allele and disease duration affect verbal learning in mild temporal lobe epilepsy. Epilepsia 46 110– 117. 10.1111/j.0013-9580.2005.15804.x 15660776 · DOI
  22. Garcia-Cabrero A. M. Guerrero-Lopez R. Giraldez B. G. Llorens-Martin M. Avila J. Serratosa J. M. (2013). Hyperexcitability and epileptic seizures in a model of frontotemporal dementia. Neurobiol. Dis. 58 200– 208. 10.1016/j.nbd.2013.06.005 23774255 · DOI
  23. Gouras G. K. Relkin N. R. Sweeney D. Munoz D. G. Mackenzie I. R. Gandy S. (1997). Increased apolipoprotein E epsilon 4 in epilepsy with senile plaques. Ann. Neurol. 41 402– 404. 10.1002/ana.410410317 9066363 · DOI
  24. Grootendorst J. Bour A. Vogel E. Kelche C. Sullivan P. M. Dodart J. C. (2005). Human apoE targeted replacement mouse lines: h-apoE4 and h-apoE3 mice differ on spatial memory performance and avoidance behavior. Behav. Brain Res. 159 1– 14. 10.1016/j.bbr.2004.09.019 15794991 · DOI · Paper page
  25. Gureviciene I. Ishchenko I. Ziyatdinova S. Jin N. Lipponen A. Gurevicius K. (2019). Characterization of epileptic spiking associated with brain amyloidosis in APP/PS1 mice. Front. Neurol. 10: 1151. 10.3389/fneur.2019.01151 31781019 PMC6861424 · DOI
  26. Hansen S. L. Sperling B. B. Sanchez C. (2004). Anticonvulsant and antiepileptogenic effects of GABAA receptor ligands in pentylenetetrazole-kindled mice. Prog. Neuropsychopharmacol. Biol. Psychiatry 28 105– 113. 10.1016/j.pnpbp.2003.09.026 14687864 · DOI
  27. Harden C. L. (2004). The apolipoprotein E epsilon (epsilon) 4 allele is important for trauma-related epilepsy. Epilepsy Curr. 4 29– 30. 10.1111/j.1535-7597.2004.04112.x 15346143 PMC324582 · DOI
  28. Hesdorffer D. C. Hauser W. A. Annegers J. F. Kokmen E. Rocca W. A. (1996). Dementia and adult-onset unprovoked seizures. Neurology 46 727– 730. 10.1212/wnl.46.3.727 8618673 · DOI
  29. Hirsch L. J. (2007). ApoE, MemorE, and EpilepsE. Epilepsy Curr. 7 149– 150. 10.1111/j.1535-7511.2007.00208.x 18049720 PMC2096726 · DOI
  30. Hunter J. M. Cirrito J. R. Restivo J. L. Kinley R. D. Sullivan P. M. Holtzman D. M. (2012). Emergence of a seizure phenotype in aged apolipoprotein epsilon 4 targeted replacement mice. Brain Res. 1467 120– 132. 10.1016/j.brainres.2012.05.048 22682924 · DOI · Paper page
  31. Imfeld P. Bodmer M. Schuerch M. Jick S. S. Meier C. R. (2013). Seizures in patients with Alzheimer’s disease or vascular dementia: a population-based nested case-control analysis. Epilepsia 54 700– 707. 10.1111/epi.12045 23215680 · DOI
  32. Irizarry M. C. Jin S. He F. Emond J. A. Raman R. Thomas R. G. (2012). Incidence of new-onset seizures in mild to moderate Alzheimer disease. Arch. Neurol. 69 368– 372. 10.1001/archneurol.2011.830 22410444 PMC3622046 · DOI
  33. Kauffman M. A. Consalvo D. Moron D. G. Lereis V. P. Kochen S. (2010). ApoE epsilon4 genotype and the age at onset of temporal lobe epilepsy: a case-control study and meta-analysis. Epilepsy Res. 90 234– 239. 10.1016/j.eplepsyres.2010.05.007 20554432 · DOI
  34. Kazim S. F. Chuang S. C. Zhao W. Wong R. K. Bianchi R. Iqbal K. (2017). Early-onset network hyperexcitability in presymptomatic Alzheimer’s disease transgenic mice is suppressed by passive immunization with anti-human APP/Abeta antibody and by mGluR5 blockade. Front. Aging Neurosci. 9: 71. 10.3389/fnagi.2017.00071 28392767 PMC5364175 · DOI · Paper page
  35. Keret O. Hoang T. D. Xia F. Rosen H. J. Yaffe K. (2020). Association of late-onset unprovoked seizures of unknown etiology with the risk of developing dementia in older veterans. JAMA Neurol. 77 710– 715. 10.1001/jamaneurol.2020.0187 32150220 PMC7063560 · DOI
  36. Lam A. D. Noebels J. (2020). Night watch on the titanic: detecting early signs of Epileptogenesis in Alzheimer disease. Epilepsy Curr. 20 369– 374. 10.1177/1535759720964775 33081517 PMC7818196 · DOI
  37. Lam A. D. Sarkis R. A. Pellerin K. R. Jing J. Dworetzky B. A. Hoch D. B. (2020). Association of epileptiform abnormalities and seizures in Alzheimer disease. Neurology 95 e2259– e2270. 10.1212/WNL.0000000000010612 32764101 PMC7713786 · DOI · Paper page
  38. Leussis M. P. Heinrichs S. C. (2006). Routine tail suspension husbandry facilitates onset of seizure susceptibility in EL mice. Epilepsia 47 801– 804. 10.1111/j.1528-1167.2006.00525.x 16650149 · DOI
  39. Liang Y. Zhou Z. Wang H. Cheng X. Zhong S. Zhao C. (2019). Association of apolipoprotein E genotypes with epilepsy risk: a systematic review and meta-analysis. Epilepsy Behav. 98(Pt A), 27– 35. 10.1016/j.yebeh.2019.06.015 31299529 · DOI · Paper page
  40. Liu C. C. Liu C. C. Kanekiyo T. Xu H. Bu G. (2013). Apolipoprotein E and Alzheimer disease: risk, mechanisms and therapy. Nat. Rev. Neurol. 9 106– 118. 10.1038/nrneurol.2012.263 23296339 PMC3726719 · DOI · Paper page
  41. Lozsadi D. A. Larner A. J. (2006). Prevalence and causes of seizures at the time of diagnosis of probable Alzheimer’s disease. Dement. Geriatr. Cogn. Disord. 22 121– 124. 10.1159/000093664 16733353 · DOI
  42. Mahley R. W. Huang Y. Weisgraber K. H. (2007). Detrimental effects of apolipoprotein E4: potential therapeutic targets in Alzheimer’s disease. Curr. Alzheimer Res. 4 537– 540. 10.2174/156720507783018334 18220516 · DOI · Paper page
  43. McAreavey M. J. Ballinger B. R. Fenton G. W. (1992). Epileptic seizures in elderly patients with dementia. Epilepsia 33 657– 660. 10.1111/j.1528-1157.1992.tb02343.x 1628580 · DOI
  44. Meller A. Kasanen I. Ruksenas O. Apanaviciene N. Baturaite Z. Voipio H. M. (2011). Refining cage change routines: comparison of cardiovascular responses to three different ways of cage change in rats. Lab. Anim. 45 167– 173. 10.1258/la.2011.010134 21498640 · DOI
  45. Mendez M. F. Catanzaro P. Doss R. C. Raul A. Frey W. H. II (1994). Seizures in Alzheimer’s disease: clinicopathologic study. J. Geriatr. Psychiatry Neurol. 7 230– 233. 10.1177/089198879400700407 7826492 · DOI
  46. Minkeviciene R. Rheims S. Dobszay M. B. Zilberter M. Hartikainen J. Fulop L. (2009). Amyloid beta-induced neuronal hyperexcitability triggers progressive epilepsy. J. Neurosci. 29 3453– 3462. 10.1523/JNEUROSCI.5215-08.2009 19295151 PMC6665248 · DOI
  47. Najm R. Jones E. A. Huang Y. (2019). Apolipoprotein E4, inhibitory network dysfunction, and Alzheimer’s disease. Mol. Neurodegener. 14: 24. 10.1186/s13024-019-0324-6 31186040 PMC6558779 · DOI · Paper page
  48. Nuriel T. Angulo S. L. Khan U. Ashok A. Chen Q. Figueroa H. Y. (2017). Neuronal hyperactivity due to loss of inhibitory tone in APOE4 mice lacking Alzheimer’s disease-like pathology. Nat. Commun. 8: 1464. 10.1038/s41467-017-01444-0 29133888 PMC5684208 · DOI · Paper page
  49. Paesler K. Xie K. Hettich M. M. Siwek M. E. Ryan D. P. Schroder S. (2015). Limited effects of an eIF2alphaS51A allele on neurological impairments in the 5xFAD mouse model of Alzheimer’s disease. Neural Plast. 2015: 825157. 10.1155/2015/825157 25883808 PMC4391319 · DOI
  50. Palop J. J. Chin J. Roberson E. D. Wang J. Thwin M. T. Bien-Ly N. (2007). Aberrant excitatory neuronal activity and compensatory remodeling of inhibitory hippocampal circuits in mouse models of Alzheimer’s disease. Neuron 55 697– 711. 10.1016/j.neuron.2007.07.025 17785178 PMC8055171 · DOI · Paper page
  51. Pandis D. Scarmeas N. (2012). Seizures in Alzheimer disease: clinical and epidemiological data. Epilepsy Curr. 12 184– 187. 10.5698/1535-7511-12.5.184 23118603 PMC3482722 · DOI
  52. Pihlajamaki M. Sperling R. A. (2009). Functional MRI assessment of task-induced deactivation of the default mode network in Alzheimer’s disease and at-risk older individuals. Behav. Neurol. 21 77– 91. 10.3233/BEN-2009-0231 19847047 PMC5450588 · DOI
  53. Ponomareva N. V. Korovaitseva G. I. Rogaev E. I. (2008). EEG alterations in non-demented individuals related to apolipoprotein E genotype and to risk of Alzheimer disease. Neurobiol. Aging 29 819– 827. 10.1016/j.neurobiolaging.2006.12.019 17293007 · DOI
  54. Qi J. Kim M. Sanchez R. Ziaee S. M. Kohtz J. D. Koh S. (2018). Enhanced susceptibility to stress and seizures in GAD65 deficient mice. PLoS One 13: e0191794. 10.1371/journal.pone.0191794 29377906 PMC5788371 · DOI
  55. Rao S. C. Dove G. Cascino G. D. Petersen R. C. (2009). Recurrent seizures in patients with dementia: frequency, seizure types, and treatment outcome. Epilepsy Behav. 14 118– 120. 10.1016/j.yebeh.2008.08.012 18782632 PMC2875670 · DOI
  56. Rasmussen S. Miller M. M. Filipski S. B. Tolwani R. J. (2011). Cage change influences serum corticosterone and anxiety-like behaviors in the mouse. J. Am. Assoc. Lab. Anim. Sci. 50 479– 483. 21838975 PMC3148651
  57. Risse S. C. Lampe T. H. Bird T. D. Nochlin D. Sumi S. M. Keenan T. (1990). Myoclonus, seizures, and paratonia in Alzheimer disease. Alzheimer Dis. Assoc. Disord. 4 217– 225. 10.1097/00002093-199040400-00003 2264979 · DOI
  58. Rodriguez G. A. Burns M. P. Weeber E. J. Rebeck G. W. (2013). Young APOE4 targeted replacement mice exhibit poor spatial learning and memory, with reduced dendritic spine density in the medial entorhinal cortex. Learn. Mem. 20 256– 266. 10.1101/lm.030031.112 23592036 PMC3630489 · DOI
  59. Romanelli M. F. Morris J. C. Ashkin K. Coben L. A. (1990). Advanced Alzheimer’s disease is a risk factor for late-onset seizures. Arch. Neurol. 47 847– 850. 10.1001/archneur.1990.00530080029006 2375689 · DOI
  60. Sarkis R. A. Dickerson B. C. Cole A. J. Chemali Z. N. (2016). Clinical and neurophysiologic characteristics of unprovoked seizures in patients diagnosed with dementia. J. Neuropsychiatry Clin. Neurosci. 28 56– 61. 10.1176/appi.neuropsych.15060143 26404175 · DOI
  61. Scarmeas N. Honig L. S. Choi H. Cantero J. Brandt J. Blacker D. (2009). Seizures in Alzheimer disease: who, when, and how common? Arch. Neurol. 66 992– 997. 10.1001/archneurol.2009.130 19667221 PMC2768279 · DOI
  62. Siwek M. E. Muller R. Henseler C. Trog A. Lundt A. Wormuth C. (2015). Altered theta oscillations and aberrant cortical excitatory activity in the 5XFAD model of Alzheimer’s disease. Neural Plast. 2015: 781731. 10.1155/2015/781731 25922768 PMC4398951 · DOI · Paper page
  63. Tai L. M. Balu D. Avila-Munoz E. Abdullah L. Thomas R. Collins N. (2017). EFAD transgenic mice as a human APOE relevant preclinical model of Alzheimer’s disease. J. Lipid Res. 58 1733– 1755. 10.1194/jlr.R076315 28389477 PMC5580905 · DOI · Paper page
  64. Tai L. M. Maldonado Weng J. LaDu M. J. Brady S. T. (2021). Relevance of transgenic mouse models for Alzheimer’s disease. Prog. Mol. Biol. Transl. Sci. 177 1– 48. 10.1016/bs.pmbts.2020.07.007 33453936 PMC8163103 · DOI
  65. Tai L. M. Thomas R. Marottoli F. M. Koster K. P. Kanekiyo T. Morris A. W. (2016). The role of APOE in cerebrovascular dysfunction. Acta Neuropathol. 131 709– 723. 10.1007/s00401-016-1547-z 26884068 PMC4837016 · DOI · Paper page
  66. Thomas R. Morris A. W. J. Tai L. M. (2017). Epidermal growth factor prevents APOE4-induced cognitive and cerebrovascular deficits in female mice. Heliyon 3: e00319. 10.1016/j.heliyon.2017.e00319 28626809 PMC5463012 · DOI
  67. Todorova M. T. Burwell T. J. Seyfried T. N. (1999). Environmental risk factors for multifactorial epilepsy in EL mice. Epilepsia 40 1697– 1707. 10.1111/j.1528-1157.1999.tb01586.x 10612332 · DOI
  68. Van Erum J. Valkenburg F. Van Dam D. De Deyn P. P. (2020). Pentylenetetrazole-induced seizure susceptibility in the Tau58/4 transgenic mouse model of tauopathy. Neuroscience 425 112– 122. 10.1016/j.neuroscience.2019.11.007 31785360 · DOI
  69. Villasana L. Acevedo S. Poage C. Raber J. (2006). Sex- and APOE isoform-dependent effects of radiation on cognitive function. Radiat. Res. 166 883– 891. 10.1667/RR0642.1 17149978 · DOI
  70. Volicer L. Smith S. Volicer B. J. (1995). Effect of seizures on progression of dementia of the Alzheimer type. Dementia 6 258– 263. 10.1159/000106956 8528372 · DOI
  71. Vossel K. A. Beagle A. J. Rabinovici G. D. Shu H. Lee S. E. Naasan G. (2013). Seizures and epileptiform activity in the early stages of Alzheimer disease. JAMA Neurol. 70 1158– 1166. 10.1001/jamaneurol.2013.136 23835471 PMC4013391 · DOI
  72. Vossel K. A. Ranasinghe K. G. Beagle A. J. Mizuiri D. Honma S. M. Dowling A. F. (2016). Incidence and impact of subclinical epileptiform activity in Alzheimer’s disease. Ann. Neurol. 80 858– 870. 10.1002/ana.24794 27696483 PMC5177487 · DOI · Paper page
  73. Westmark C. J. Westmark P. R. Malter J. S. (2010). Alzheimer’s disease and down syndrome rodent models exhibit audiogenic seizures. J. Alzheimers Dis. 20 1009– 1013. 10.3233/JAD-2010-100087 20413855 PMC2915889 · DOI
  74. Yagi H. Takamura Y. Yoneda T. Konno D. Akagi Y. Yoshida K. (2005). Vlgr1 knockout mice show audiogenic seizure susceptibility. J. Neurochem. 92 191– 202. 10.1111/j.1471-4159.2004.02875.x 15606908 · DOI
  75. Zaldua S. Damen F. C. Pisharody R. Thomas R. Fan K. D. Ekkurthi G. K. (2020). Epidermal growth factor treatment of female mice that express APOE4 at an age of advanced pathology mitigates behavioral and cerebrovascular dysfunction. Heliyon 6: e03919. 10.1016/j.heliyon.2020.e03919 32478184 PMC7251379 · DOI

Cited by

Sorted by citations

Authors
Lamoureux, L., Marottoli, F. M., Tseng, K. Y., & Tai, L. M.
Venue
Frontiers in Cell and Developmental Biology
Published
2021-03-16
Volume
9
ISSN
2296-634X
Cited by
23
References
5
Funders
National Institutes of Health

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