{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,20]],"date-time":"2026-09-20T03:20:34Z","timestamp":1789874434590,"version":"4.0.1"},"reference-count":107,"publisher":"Oxford University Press (OUP)","issue":"23","license":[{"start":{"date-parts":[[2024,9,26]],"date-time":"2024-09-26T00:00:00Z","timestamp":1727308800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["NS098243"],"award-info":[{"award-number":["NS098243"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["AG017617"],"award-info":[{"award-number":["AG017617"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2024,11,20]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Mutations in PSEN1 were first discovered as a cause of Alzheimer's disease (AD) in 1995, yet the mechanism(s) by which the mutations cause disease still remains unknown. The generation of novel mouse models assessing the effects of different mutations could aid in this endeavor. Here we report on transgenic mouse lines made with the \u0394440 PSEN1 mutation that causes AD with parkinsonism:\u2014 two expressing the un-tagged human protein and two expressing a HA-tagged version. Detailed characterization of these lines showed that Line 305 in particular, which expresses the untagged protein, develops age-dependent memory deficits and pathologic features, many of which are consistent with features found in AD. Key behavioral and physiological alterations found in the novel 305 line included an age-dependent deficit in spontaneous alternations in the Y-maze, a decrease in exploration of the center of an open field box, a decrease in the latency to fall on a rotarod, a reduction in synaptic strength and pair-pulse facilitation by electrophysiology, and profound alterations to cerebral blood flow regulation. The pathologic alterations found in the line included, significant neuronal loss in the hippocampus and cortex, astrogliosis, and changes in several proteins involved in synaptic and mitochondrial function, Ca2+ regulation, and autophagy. Taken together, these findings suggest that the transgenic lines will be useful for the investigation of AD pathogenesis.<\/jats:p>","DOI":"10.1093\/hmg\/ddae139","type":"journal-article","created":{"date-parts":[[2024,9,26]],"date-time":"2024-09-26T08:08:19Z","timestamp":1727338099000},"page":"2051-2070","source":"Crossref","is-referenced-by-count":1,"title":["Pathophysiologic abnormalities in transgenic mice carrying the Alzheimer disease <i>PSEN1<\/i> \u0394440 mutation"],"prefix":"10.1093","volume":"33","author":[{"given":"Peyton E","family":"Fuller","sequence":"first","affiliation":[{"name":"Center for Biomedical Engineering and Technology, University of Maryland School of Medicine , 660 West Redwood Street, Baltimore, MD 21201,","place":["United States"]},{"name":"Department of Neurobiology, University of Maryland School of Medicine , Baltimore, MD 21201,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Victoria L","family":"Collis","sequence":"additional","affiliation":[{"name":"Center for Biomedical Engineering and Technology, University of Maryland School of Medicine , 660 West Redwood Street, Baltimore, MD 21201,","place":["United States"]},{"name":"Department of Neurobiology, University of Maryland School of Medicine , Baltimore, MD 21201,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pallavi","family":"Sharma","sequence":"additional","affiliation":[{"name":"Center for Biomedical Engineering and Technology, University of Maryland School of Medicine , 660 West Redwood Street, Baltimore, MD 21201,","place":["United States"]},{"name":"Department of Neurobiology, University of Maryland School of Medicine , Baltimore, MD 21201,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Angelina M","family":"Burkett","sequence":"additional","affiliation":[{"name":"Center for Biomedical Engineering and Technology, University of Maryland School of Medicine , 660 West Redwood Street, Baltimore, MD 21201,","place":["United States"]},{"name":"Department of Neurobiology, University of Maryland School of Medicine , Baltimore, MD 21201,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shaoteng","family":"Wang","sequence":"additional","affiliation":[{"name":"Center for Biomedical Engineering and Technology, University of Maryland School of Medicine , 660 West Redwood Street, Baltimore, MD 21201,","place":["United States"]},{"name":"Department of Neurobiology, University of Maryland School of Medicine , Baltimore, MD 21201,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kyle A","family":"Brown","sequence":"additional","affiliation":[{"name":"Department of Psychiatry, University of Maryland School of Medicine , 685 W Baltimore Street, Baltimore, MD 21201,","place":["United States"]},{"name":"Department of Pharmacology, University of Maryland School of Medicine , Baltimore, MD 21201,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nick","family":"Weir","sequence":"additional","affiliation":[{"name":"Department of Physiology, University of Maryland School of Medicine , 660 W Redwood Street, Baltimore, MD 21201,","place":["United States"]},{"name":"Laboratory of Neurovascular Interactions , Center for Biomedical Engineering and Technology, , Baltimore, MD","place":["USA"]},{"name":"University of Maryland School of Medicine , Center for Biomedical Engineering and Technology, , Baltimore, MD","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chris N","family":"Goulbourne","sequence":"additional","affiliation":[{"name":"Center for Dementia Research, Nathan S. Kline Institute , 140 Old Orangeburg Road, Orangeburg, NY 10962,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ralph A","family":"Nixon","sequence":"additional","affiliation":[{"name":"Center for Dementia Research, Nathan S. Kline Institute , 140 Old Orangeburg Road, Orangeburg, NY 10962,","place":["United States"]},{"name":"NYU Neuroscience Institute, New York University Grossman School of Medicine , New York, NY 10016,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas A","family":"Longden","sequence":"additional","affiliation":[{"name":"Department of Physiology, University of Maryland School of Medicine , 660 W Redwood Street, Baltimore, MD 21201,","place":["United States"]},{"name":"Laboratory of Neurovascular Interactions , Center for Biomedical Engineering and Technology, , Baltimore, MD","place":["USA"]},{"name":"University of Maryland School of Medicine , Center for Biomedical Engineering and Technology, , Baltimore, MD","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Todd D","family":"Gould","sequence":"additional","affiliation":[{"name":"Department of Neurobiology, University of Maryland School of Medicine , Baltimore, MD 21201,","place":["United States"]},{"name":"Department of Psychiatry, University of Maryland School of Medicine , 685 W Baltimore Street, Baltimore, MD 21201,","place":["United States"]},{"name":"Department of Pharmacology, University of Maryland School of Medicine , Baltimore, MD 21201,","place":["United States"]},{"name":"Veterans Affairs Maryland Health Care System , Baltimore, MD 21201,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1740-5309","authenticated-orcid":false,"given":"Mervyn J","family":"Monteiro","sequence":"additional","affiliation":[{"name":"Center for Biomedical Engineering and Technology, University of Maryland School of Medicine , 660 West Redwood Street, Baltimore, MD 21201,","place":["United States"]},{"name":"Department of Neurobiology, University of Maryland School of Medicine , Baltimore, MD 21201,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2024,9,26]]},"reference":[{"key":"2024112017454433700_ref1","doi-asserted-by":"crossref","first-page":"733","DOI":"10.1016\/j.jalz.2016.01.012","article-title":"Molecular genetics of early-onset Alzheimer's disease revisited","volume":"12","author":"Cacace","year":"2016","journal-title":"Alzheimers Dement"},{"key":"2024112017454433700_ref2","doi-asserted-by":"crossref","first-page":"412","DOI":"10.1038\/s41588-022-01024-z","article-title":"New insights into the genetic etiology of Alzheimer's disease and related dementias","volume":"54","author":"Bellenguez","year":"2022","journal-title":"Nat Genet"},{"key":"2024112017454433700_ref3","doi-asserted-by":"crossref","first-page":"459","DOI":"10.1083\/jcb.201709069","article-title":"Microglia in Alzheimer's disease","volume":"217","author":"Hansen","year":"2018","journal-title":"J Cell 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