*Result*: Genome-wide consensus transcriptional signatures identify synaptic pruning linking Alzheimer's disease and epilepsy.

Genome-wide consensus transcriptional signatures identify synaptic pruning linking Alzheimer's disease and epilepsy.

Li H; Department of Neurosurgery, The First Affiliated Hospital of Shantou University Medical College, Shantou, Guangdong, China.; Brain Function and Disease Laboratory, Shantou University Medical College, Shantou, Guangdong, China.; Department of Pharmacology, Shantou University Medical College, Shantou, Guangdong, China.; Program in Computational Biology and Biomedical Informatics, Yale University, New Haven, Connecticut, USA., Xie Z; Program in Computational Biology and Biomedical Informatics, Yale University, New Haven, Connecticut, USA., Tian Y; Program in Computational Biology and Biomedical Informatics, Yale University, New Haven, Connecticut, USA., Zhou R; Program in Computational Biology and Biomedical Informatics, Yale University, New Haven, Connecticut, USA., Yang Y; Program in Computational Biology and Biomedical Informatics, Yale University, New Haven, Connecticut, USA., Lin B; Department of Neurosurgery, The First Affiliated Hospital of Shantou University Medical College, Shantou, Guangdong, China.; Brain Function and Disease Laboratory, Shantou University Medical College, Shantou, Guangdong, China.; Department of Pharmacology, Shantou University Medical College, Shantou, Guangdong, China.; Pain and Related Diseases Research Laboratory, Shantou University Medical College, Shantou, Guangdong, China., Chen S; Department of Neurosurgery, The First Affiliated Hospital of Shantou University Medical College, Shantou, Guangdong, China.; Brain Function and Disease Laboratory, Shantou University Medical College, Shantou, Guangdong, China.; Department of Pharmacology, Shantou University Medical College, Shantou, Guangdong, China.; Pain and Related Diseases Research Laboratory, Shantou University Medical College, Shantou, Guangdong, China., Wu J; Department of Neurosurgery, The First Affiliated Hospital of Shantou University Medical College, Shantou, Guangdong, China.; Brain Function and Disease Laboratory, Shantou University Medical College, Shantou, Guangdong, China.; Department of Pharmacology, Shantou University Medical College, Shantou, Guangdong, China., Deng Z; Department of Neurosurgery, The First Affiliated Hospital of Shantou University Medical College, Shantou, Guangdong, China.; Brain Function and Disease Laboratory, Shantou University Medical College, Shantou, Guangdong, China.; Department of Pharmacology, Shantou University Medical College, Shantou, Guangdong, China.; Pain and Related Diseases Research Laboratory, Shantou University Medical College, Shantou, Guangdong, China., Li J; Department of Neurosurgery, The First Affiliated Hospital of Shantou University Medical College, Shantou, Guangdong, China.; Brain Function and Disease Laboratory, Shantou University Medical College, Shantou, Guangdong, China.; Department of Pharmacology, Shantou University Medical College, Shantou, Guangdong, China.; Pain and Related Diseases Research Laboratory, Shantou University Medical College, Shantou, Guangdong, China., Chen M; Department of Biotechnology and Food Engineering, Guangdong Technion - Israel Institute of Technology, Shantou, Guangdong, China., Liu X; Department of Biotechnology and Food Engineering, Guangdong Technion - Israel Institute of Technology, Shantou, Guangdong, China., Sun Y; Department of Biotechnology and Food Engineering, Guangdong Technion - Israel Institute of Technology, Shantou, Guangdong, China., Wei N; Department of Neurosurgery, The First Affiliated Hospital of Shantou University Medical College, Shantou, Guangdong, China., Huang B; Department of Neurosurgery, The First Affiliated Hospital of Shantou University Medical College, Shantou, Guangdong, China. bhuangfd@stu.edu.cn.; Brain Function and Disease Laboratory, Shantou University Medical College, Shantou, Guangdong, China. bhuangfd@stu.edu.cn.; Department of Pharmacology, Shantou University Medical College, Shantou, Guangdong, China. bhuangfd@stu.edu.cn.; Pain and Related Diseases Research Laboratory, Shantou University Medical College, Shantou, Guangdong, China. bhuangfd@stu.edu.cn., Ji X; Department of Neurosurgery, The First Affiliated Hospital of Shantou University Medical College, Shantou, Guangdong, China. xyji@stu.edu.cn.; Brain Function and Disease Laboratory, Shantou University Medical College, Shantou, Guangdong, China. xyji@stu.edu.cn.; Department of Pharmacology, Shantou University Medical College, Shantou, Guangdong, China. xyji@stu.edu.cn.; Pain and Related Diseases Research Laboratory, Shantou University Medical College, Shantou, Guangdong, China. xyji@stu.edu.cn.

Molecular psychiatry [Mol Psychiatry] 2026 Mar; Vol. 31 (3), pp. 1774-1784. Date of Electronic Publication: 2025 Oct 26.

Journal Article

English

Publisher: Nature Publishing Group Specialist Journals Country of Publication: England NLM ID: 9607835 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1476-5578 (Electronic) Linking ISSN: 13594184 NLM ISO Abbreviation: Mol Psychiatry Subsets: MEDLINE

Publication: 2000- : Houndmills, Basingstoke, UK : Nature Publishing Group Specialist Journals
Original Publication: Houndmills, Hampshire, UK ; New York, NY : Stockton Press, c1996-

Alzheimer Disease*/genetics , Alzheimer Disease*/metabolism , Epilepsy*/genetics , Epilepsy*/metabolism, Microglia/metabolism ; Synapses/metabolism ; Synapses/genetics ; Gene Regulatory Networks/genetics ; Transcriptome/genetics ; Membrane Glycoproteins/metabolism ; Membrane Glycoproteins/genetics ; Genome-Wide Association Study/methods ; Receptors, Immunologic/metabolism ; Receptors, Immunologic/genetics ; Gene Expression Profiling/methods ; Epilepsy, Temporal Lobe/genetics ; Epilepsy, Temporal Lobe/metabolism ; tau Proteins/metabolism ; tau Proteins/genetics ; Humans ; Animals ; Mice ; Mice, Transgenic ; Disease Models, Animal ; Male ; Female ; Membrane Proteins ; Adaptor Proteins, Signal Transducing

Vossel KA, Beagle AJ, Rabinovici GD, Shu H, Lee SE, Naasan G, et al. Seizures and epileptiform activity in the early stages of Alzheimer disease. JAMA Neurol. 2013;70:1158–66. (PMID: 238354714013391)
Palop JJ, Mucke L. Epilepsy and cognitive impairments in Alzheimer disease. Arch Neurol. 2009;66:435–40. (PMID: 192041492812914)
Fang Y, Si X, Wang J, Wang Z, Chen Y, Liu Y, et al. Alzheimer disease and epilepsy. Neurology. 2023;101:e399–409. (PMID: 3722543210435057)
Prince M, Wimo A, Guerchet M, Ali GC, Wu YT, Prina M. World Alzheimer Report 2015. The global impact of dementia: an analysis of prevalence, incidence, cost and trends. Alzheimer’s Disease International; 2015. http://www.alz.co.uk/research/world-report-2015 .
Ngugi AK, Bottomley C, Kleinschmidt I, Sander JW, Newton CR. Estimation of the burden of active and life-time epilepsy: a meta-analytic approach. Epilepsia. 2010;51:883–90. (PMID: 200675073410521)
Mendez MF, Lim GTH. Seizures in Elderly Patients with Dementia. Drugs Aging. 2003;20:791–803. (PMID: 12964886)
Pandis D, Scarmeas N. Seizures in Alzheimer disease: clinical and epidemiological data: seizures in Alzheimer disease. Epilepsy Curr. 2012;12:184–7. (PMID: 231186033482722)
Leitner D, Pires G, Kavanagh T, Kanshin E, Askenazi M, Ueberheide B, et al. Similar brain proteomic signatures in Alzheimer’s disease and epilepsy. Acta Neuropathol. 2024;147:27. (PMID: 3828953910827928)
Tombini M, Assenza G, Ricci L, Lanzone J, Boscarino M, Vico C, et al. Temporal lobe epilepsy and Alzheimer’s disease: from preclinical to clinical evidence of a strong association. J Alzheimers Dis Rep. 2021;5:243–61. (PMID: 341137828150253)
Johnson EL, Krauss GL, Lee AK, Schneider ALC, Dearborn JL, Kucharska-Newton AM, et al. Association between midlife risk factors and late-onset epilepsy: results from the atherosclerosis risk in communities study. JAMA Neurol. 2018;75:1375–82. (PMID: 300391756248112)
Stefanidou M, Beiser AS, Himali JJ, Peng TJ, Devinsky O, Seshadri S, et al. Bi-directional association between epilepsy and dementia. Neurology. 2020;95:e3241–7. (PMID: 330975997836659)
Noebels J. A perfect storm: converging paths of epilepsy and Alzheimer’s dementia intersect in the hippocampal formation. Epilepsia. 2011;52:39–46. (PMID: 212145383058398)
Gourmaud S, Shou H, Irwin DJ, Sansalone K, Jacobs LM, Lucas TH, et al. Alzheimer-like amyloid and tau alterations associated with cognitive deficit in temporal lobe epilepsy. Brain. 2020;143:191–209. (PMID: 318343536935754)
Tai XY, Koepp M, Duncan JS, Fox N, Thompson P, Baxendale S, et al. Hyperphosphorylated tau in patients with refractory epilepsy correlates with cognitive decline: a study of temporal lobe resections. Brain. 2016;139:2441–55. (PMID: 274979245926008)
Nelson PT, Schmitt FA, Lin Y, Abner EL, Jicha GA, Patel E, et al. Hippocampal sclerosis in advanced age: clinical and pathological features. Brain. 2011;134:1506–18. (PMID: 215967743097889)
Zou Y, Wang C, Li H, Zhong M, Lin J, Hu Y, et al. Epileptic seizures induced by pentylenetetrazole kindling accelerate Alzheimer-like neuropathology in 5×FAD mice. Front Pharmacol. 2024;15:1500105. (PMID: 3954506611560768)
Watts ME, Pocock R, Claudianos C. Brain energy and oxygen metabolism: emerging role in normal function and disease. Front Mol Neurosci. 2018;11:216. (PMID: 299883686023993)
Born HA. Seizures in Alzheimer’s disease. Neuroscience. 2015;286:251–63. (PMID: 25484360)
Toniolo S, Sen A, Husain M. Modulation of brain hyperexcitability: potential new therapeutic approaches in Alzheimer’s disease. Int J Mol Sci. 2020;21:9318. (PMID: 332974607730926)
Dudok B, Klein PM, Soltesz I. Toward understanding the diverse roles of perisomatic interneurons in epilepsy. Epilepsy Curr. 2022;22:54–60. (PMID: 35233202)
Verret L, Mann EO, Hang GB, Barth AMI, Cobos I, Ho K, et al. Inhibitory interneuron deficit links altered network activity and cognitive dysfunction in Alzheimer model. Cell. 2012;149:708–21. (PMID: 225414393375906)
Palop JJ, Chin J, Roberson ED, Wang J, Thwin MT, Bien-Ly N, et al. Aberrant excitatory neuronal activity and compensatory remodeling of inhibitory hippocampal circuits in mouse models of Alzheimer’s disease. Neuron. 2007;55:697–711. (PMID: 177851788055171)
Targa Dias Anastacio H, Matosin N, Ooi L. Neuronal hyperexcitability in Alzheimer’s disease: what are the drivers behind this aberrant phenotype? Transl Psychiatry. 2022;12:1–14.
Liew Y, Retinasamy T, Arulsamy A, Ali I, Jones NC, O’Brien TJ, et al. Neuroinflammation: a common pathway in Alzheimer’s disease and epilepsy. J Alzheimer’s Dis. 2023;94:S253–65.
Kalyvas AC, Dimitriou M, Ioannidis P, Grigoriadis N, Afrantou T. Alzheimer’s disease and epilepsy: exploring shared pathways and promising biomarkers for future treatments. J Clin Med. 2024;13:3879. (PMID: 3899944511242231)
Giorgi FS, Saccaro LF, Busceti CL, Biagioni F, Fornai F. Epilepsy and Alzheimer’s Disease: Potential mechanisms for an association. Brain Res Bull. 2020;160:107–20. (PMID: 32380189)
Bosco F, Guarnieri L, Rania V, Palma E, Citraro R, Corasaniti MT, et al. Antiseizure medications in Alzheimer’s disease from preclinical to clinical evidence. Int J Mol Sci. 2023;24:12639. (PMID: 3762882110454935)
Srivastava PK, Bagnati M, Delahaye-Duriez A, Ko JH, Rotival M, Langley SR, et al. Genome-wide analysis of differential RNA editing in epilepsy. Genome Res. 2017;27:440–50. (PMID: 282500185340971)
Matarin M, Salih DA, Yasvoina M, Cummings DM, Guelfi S, Liu W, et al. A Genome-wide gene-expression analysis and database in transgenic mice during development of amyloid or tau pathology. Cell Rep. 2015;10:633–44. (PMID: 25620700)
Castanho I, Murray TK, Hannon E, Jeffries A, Walker E, Laing E, et al. Transcriptional signatures of tau and amyloid neuropathology. Cell Rep. 2020;30:2040–54.e5. (PMID: 320490307016505)
Johnson MR, Behmoaras J, Bottolo L, Krishnan ML, Pernhorst K, Santoscoy PLM, et al. Systems genetics identifies Sestrin 3 as a regulator of a proconvulsant gene network in human epileptic hippocampus. Nat Commun. 2015;6:6031. (PMID: 256158864627576)
Wan YW, Al-Ouran R, Mangleburg CG, Perumal TM, Lee TV, Allison K, et al. Meta-analysis of the Alzheimer’s disease human brain transcriptome and functional dissection in mouse models. Cell Rep. 2020;32:107908. (PMID: 326682557428328)
Miller JA, Horvath S, Geschwind DH. Divergence of human and mouse brain transcriptome highlights Alzheimer disease pathways. Proc Natl Acad Sci. 2010;107:12698–703. (PMID: 206160002906579)
Langfelder P, Horvath S. WGCNA: an R package for weighted correlation network analysis. BMC Bioinformatics. 2008;9:559. (PMID: 191140082631488)
Wu T, Hu E, Xu S, Chen M, Guo P, Dai Z, et al. clusterProfiler 4.0: A universal enrichment tool for interpreting omics data. The Innovation. 2021;2:100141. (PMID: 345577788454663)
Langfelder P, Luo R, Oldham MC, Horvath S. Is my network module preserved and reproducible? PLOS Comput Biol. 2011;7:e1001057. (PMID: 212837763024255)
Szklarczyk D, Nastou K, Koutrouli M, Kirsch R, Mehryary F, Hachilif R, et al. The STRING database in 2025: protein networks with directionality of regulation. Nucleic Acids Res. 2025;53:D730–7. (PMID: 3955818311701646)
Huynh-Thu VA, Irrthum A, Wehenkel L, Geurts P. Inferring regulatory networks from expression data using tree-based methods. PLOS ONE. 2010;5:e12776. (PMID: 209271932946910)
Chen ZP, Wang S, Zhao X, Fang W, Wang Z, Ye H, et al. Lipid-accumulated reactive astrocytes promote disease progression in epilepsy. Nat Neurosci. 2023;26:542–54. (PMID: 36941428)
Mathys H, Davila-Velderrain J, Peng Z, Gao F, Mohammadi S, Young JZ, et al. Single-cell transcriptomic analysis of Alzheimer’s disease. Nature. 2019;570:332–7. (PMID: 310426976865822)
Hao Y, Stuart T, Kowalski MH, Choudhary S, Hoffman P, Hartman A, et al. Dictionary learning for integrative, multimodal and scalable single-cell analysis. Nat Biotechnol. 2024;42:293–304. (PMID: 37231261)
Tuddenham JF, Taga M, Haage V, Marshe VS, Roostaei T, White C, et al. A cross-disease resource of living human microglia identifies disease-enriched subsets and tool compounds recapitulating microglial states. Nat Neurosci. 2024;27:2521–37. (PMID: 3940695012094270)
Martins-Ferreira R, Calafell-Segura J, Leal B, Rodríguez-Ubreva J, Martínez-Saez E, Mereu E, et al. The Human Microglia Atlas (HuMicA) unravels changes in disease-associated microglia subsets across neurodegenerative conditions. Nat Commun. 2025;16:739. (PMID: 3982000411739505)
Stimberg M, Brette R, Goodman DF. Brian 2, an intuitive and efficient neural simulator. eLife. 2019;8:e47314. (PMID: 314298246786860)
Liu Y, Grigorovsky V, Bardakjian B. Excitation and inhibition balance underlying epileptiform activity. IEEE Trans Biomed Eng. 2020;67:2473–81. (PMID: 31902751)
Penn Y, Segal M, Moses E. Network synchronization in hippocampal neurons. Proc Natl Acad Sci. 2016;113:3341–6. (PMID: 269610004812773)
Vezzani A, French J, Bartfai T, Baram TZ. The role of inflammation in epilepsy. Nat Rev Neurol. 2011;7:31–40. (PMID: 21135885)
Heneka MT, Golenbock DT, Latz E. Innate immunity in Alzheimer’s disease. Nat Immunol. 2015;16:229–36. (PMID: 25689443)
Pekny M, Pekna M. Astrocyte reactivity and reactive astrogliosis: costs and benefits. Physiol Rev. 2014;94:1077–98. (PMID: 25287860)
Onyango IG, Jauregui GV, Čarná M, Bennett JP, Stokin GB. Neuroinflammation in Alzheimer’s disease. Biomedicines. 2021;9:524. (PMID: 340671738150909)
Vezzani A, Viviani B. Neuromodulatory properties of inflammatory cytokines and their impact on neuronal excitability. Neuropharmacology. 2015;96:70–82. (PMID: 25445483)
van Vliet EA, Aronica E, Gorter JA. Blood–brain barrier dysfunction, seizures and epilepsy. Semin Cell Dev Biol. 2015;38:26–34. (PMID: 25444846)
Zlokovic BV. Neurovascular pathways to neurodegeneration in Alzheimer’s disease and other disorders. Nat Rev Neurosci. 2011;12:723–38. (PMID: 220480624036520)
Kopczynska M, Zelek WM, Vespa S, Touchard S, Wardle M, Loveless S, et al. Complement system biomarkers in epilepsy. Seizure. 2018;60:1–7. (PMID: 29857269)
Veerhuis R, Nielsen HM, Tenner AJ. Complement in the brain. Mol Immunol. 2011;48:1592–603. (PMID: 215460883142281)
Roussos P, Katsel P, Fam P, Tan W, Purohit DP, Haroutunian V. The triggering receptor expressed on myeloid cells 2 (TREM2) is associated with enhanced inflammation, neuropathological lesions and increased risk for Alzheimer’s dementia. Alzheimers Dement. 2015;11:1163–70. (PMID: 25499537)
Ma J, Jiang T, Tan L, Yu JT. TYROBP in Alzheimer’s disease. Mol Neurobiol. 2015;51:820–6. (PMID: 25052481)
Jonsson T, Stefansson H, Steinberg S, Jonsdottir I, Jonsson PV, Snaedal J, et al. Variant of TREM2 associated with the risk of Alzheimer’s disease. N Engl J Med. 2013;368:107–16. (PMID: 23150908)
Stevens B, Allen NJ, Vazquez LE, Howell GR, Christopherson KS, Nouri N, et al. The classical complement cascade mediates CNS synapse elimination. Cell. 2007;131:1164–78. (PMID: 18083105)
Haure-Mirande JV, Audrain M, Ehrlich ME, Gandy S. Microglial TYROBP/DAP12 in Alzheimer’s disease: transduction of physiological and pathological signals across TREM2. Mol Neurodegener. 2022;17:55. (PMID: 360028549404585)
Haure-Mirande JV, Audrain M, Fanutza T, Kim SH, Klein WL, Glabe C, et al. Deficiency of TYROBP, an adapter protein for TREM2 and CR3 receptors, is neuroprotective in a mouse model of early Alzheimer’s pathology. Acta Neuropathol. 2017;134:769–88. (PMID: 286122905645450)
Audrain M, Haure-Mirande JV, Wang M, Kim SH, Fanutza T, Chakrabarty P, et al. Integrative approach to sporadic Alzheimer’s disease: deficiency of TYROBP in a tauopathy mouse model reduces C1q and normalizes clinical phenotype while increasing spread and state of phosphorylation of tau. Mol Psychiatry. 2019;24:1383–97. (PMID: 30283031)
Haure-Mirande JV, Wang M, Audrain M, Fanutza T, Kim SH, Heja S, et al. Integrative approach to sporadic Alzheimer’s disease: deficiency of TYROBP in cerebral Aβ amyloidosis mouse normalizes clinical phenotype and complement subnetwork molecular pathology without reducing Aβ burden. Mol Psychiatry. 2019;24:431–46. (PMID: 30283032)
Hu Y, Qi H, Yang J, Wang F, Peng X, Chen X, et al. Wogonin mitigates microglia-mediated synaptic over-pruning and cognitive impairment following epilepsy. Phytomedicine. 2024;135:156222. (PMID: 39547095)
Bie B, Wu J, Foss JF, Naguib M. Activation of mGluR1 mediates C1q-dependent microglial phagocytosis of glutamatergic synapses in Alzheimer’s rodent models. Mol Neurobiol. 2019;56:5568–85. (PMID: 306522666615956)
Wu J, Bie B, Foss JF, Naguib M. Amyloid fibril–induced astrocytic glutamate transporter disruption contributes to complement C1q-mediated microglial pruning of glutamatergic synapses. Mol Neurobiol. 2020;57:2290–300. (PMID: 32008166)
Bosco DB, Kremen V, Haruwaka K, Zhao S, Wang L, Ebner BA, et al. Microglial TREM2 promotes phagocytic clearance of damaged neurons after status epilepticus. Brain Behav Immun. 2025;123:540–55. (PMID: 39353548)
Andoh M, Ikegaya Y, Koyama R. Synaptic pruning by microglia in epilepsy. J Clin Med. 2019;8:2170. (PMID: 318180186947403)
Yuan P, Zhang M, Tong L, Morse TM, McDougal RA, Ding H, et al. PLD3 affects axonal spheroids and network defects in Alzheimer’s disease. Nature. 2022;612:328–37. (PMID: 364509919729106)
Stefanescu RA, Shivakeshavan RG, Talathi SS. Computational models of epilepsy. Seizure. 2012;21:748–59. (PMID: 22995680)
Luo L. Architectures of neuronal circuits. Science. 2021;373:eabg7285. (PMID: 345168448916593)
Neri S, Mastroianni G, Gardella E, Aguglia U, Rubboli G. Epilepsy in neurodegenerative diseases. Epileptic Disord. 2022;24:249–73. (PMID: 35596580)
Chen ZP, Zhao X, Wang S, Cai R, Liu Q, Ye H, et al. GABA-dependent microglial elimination of inhibitory synapses underlies neuronal hyperexcitability in epilepsy. Nat Neurosci. 2025;28:1404–17. (PMID: 40425792)
Dejanovic B, Wu T, Tsai MC, Graykowski D, Gandham VD, Rose CM, et al. Complement C1q-dependent excitatory and inhibitory synapse elimination by astrocytes and microglia in Alzheimer’s disease mouse models. Nat Aging. 2022;2:837–50. (PMID: 3711850410154216)
Fan J, Dong X, Tang Y, Wang X, Lin D, Gong L, et al. Preferential pruning of inhibitory synapses by microglia contributes to alteration of the balance between excitatory and inhibitory synapses in the hippocampus in temporal lobe epilepsy. CNS Neurosci Ther. 2023;29:2884–900. (PMID: 3707293210493672)
Holden SS, Grandi FC, Aboubakr O, Higashikubo B, Cho FS, Chang AH, et al. Complement factor C1q mediates sleep spindle loss and epileptic spikes after mild brain injury. Science. 2021;373:eabj2685. (PMID: 345167968750918)
Chu Y, Jin X, Parada I, Pesic A, Stevens B, Barres B, et al. Enhanced synaptic connectivity and epilepsy in C1q knockout mice. Proc Natl Acad Sci. 2010;107:7975–80. (PMID: 203752782867906)
Ma Y, Ramachandran A, Ford N, Parada I, Prince DA. Remodeling of dendrites and spines in the C1q knockout model of genetic epilepsy. Epilepsia. 2013;54:1232–9. (PMID: 236211543700654)

82201629 National Science Foundation of China | Young Scientists Fund

0 (Membrane Glycoproteins)
0 (Receptors, Immunologic)
0 (TYROBP protein, human)
0 (tau Proteins)
0 (TREM2 protein, human)
0 (Membrane Proteins)
0 (Adaptor Proteins, Signal Transducing)

Date Created: 20251027 Date Completed: 20260219 Latest Revision: 20260219

20260219

10.1038/s41380-025-03318-0

41139712

MEDLINE