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Here, we investigated in young ArcticA\u03b2 mice whether <jats:styled-content style=\"fixed-case\">AD<\/jats:styled-content>\u2010like pathology renders neuronal networks more susceptible to the development of acquired epilepsy induced by unilateral intrahippocampal injection of kainic acid (<jats:styled-content style=\"fixed-case\">IHK<\/jats:styled-content>). In this temporal lobe epilepsy model, <jats:styled-content style=\"fixed-case\">IHK<\/jats:styled-content> induces a status epilepticus followed after two weeks by spontaneous recurrent seizures (<jats:styled-content style=\"fixed-case\">SRS<\/jats:styled-content>). ArcticA\u03b2 mice exhibited more severe status epilepticus and early onset of <jats:styled-content style=\"fixed-case\">SRS<\/jats:styled-content>. This hyperexcitable phenotype was characterized in <jats:styled-content style=\"fixed-case\">CA<\/jats:styled-content>1 neurons by decreased synaptic strength, increased kainic acid\u2010induced <jats:styled-content style=\"fixed-case\">LTP<\/jats:styled-content> and reduced frequency of spontaneous inhibitory currents. However, no difference in neurodegeneration, neuroinflammation, axonal reorganization or adult neurogenesis was observed in ArcticA\u03b2 mice compared to wild\u2010type littermates following <jats:styled-content style=\"fixed-case\">IHK<\/jats:styled-content>\u2010induced epileptogenesis. Neuropeptide Y (<jats:styled-content style=\"fixed-case\">NPY<\/jats:styled-content>) expression was reduced at baseline and its <jats:styled-content style=\"fixed-case\">IHK<\/jats:styled-content>\u2010induced elevation in mossy fibres and granule cells was attenuated. However, although this alteration might underlie premature seizure onset, neutralization of soluble A\u03b2 species by intracerebroventricular A\u03b2\u2010specific antibody application mitigated the hyperexcitable phenotype of ArcticA\u03b2 mice and prevented early <jats:styled-content style=\"fixed-case\">SRS<\/jats:styled-content> onset. Therefore, the development of seizures at early stages of <jats:styled-content style=\"fixed-case\">AD<\/jats:styled-content> is mediated primarily by A\u03b2 species causing widespread changes in synaptic function.<\/jats:p>","DOI":"10.1111\/ejn.13983","type":"journal-article","created":{"date-parts":[[2018,6,4]],"date-time":"2018-06-04T07:30:56Z","timestamp":1528097456000},"page":"1534-1562","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":17,"title":["Contribution of early Alzheimer's disease\u2010related pathophysiology to the development of acquired epilepsy"],"prefix":"10.1111","volume":"47","author":[{"given":"Tilo","family":"Gschwind","sequence":"first","affiliation":[{"name":"Institute of Pharmacology and Toxicology University of Zurich  Zurich Switzerland"},{"name":"Neuroscience Center Zurich University of Zurich and ETH Zurich  Zurich Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carlos","family":"Lafourcade","sequence":"additional","affiliation":[{"name":"Institute of Pharmacology and Toxicology University of Zurich  Zurich Switzerland"},{"name":"Laboratorio de Neurociencias Universidad de los Andes  Santiago Chile"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tim","family":"Gfeller","sequence":"additional","affiliation":[{"name":"Institute of Pharmacology and Toxicology University of Zurich  Zurich Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mariana","family":"Zaichuk","sequence":"additional","affiliation":[{"name":"Institute of Pharmacology and Toxicology University of Zurich  Zurich Switzerland"},{"name":"Neuroscience Center Zurich University of Zurich and ETH Zurich  Zurich Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lukas","family":"Rambousek","sequence":"additional","affiliation":[{"name":"Institute of Experimental Immunology University of Zurich  Zurich Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Irene","family":"Knuesel","sequence":"additional","affiliation":[{"name":"Institute of Pharmacology and Toxicology University of Zurich  Zurich Switzerland"},{"name":"Roche Pharmaceutical Research and Early Development NORD Discovery &amp; 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