{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T01:41:49Z","timestamp":1760060509943,"version":"build-2065373602"},"reference-count":30,"publisher":"MDPI AG","issue":"17","license":[{"start":{"date-parts":[[2025,8,30]],"date-time":"2025-08-30T00:00:00Z","timestamp":1756512000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Instituto de Salud Carlos III, Madrid, Spain","award":["INT24\/00060","CSI23\/24"],"award-info":[{"award-number":["INT24\/00060","CSI23\/24"]}]},{"name":"Institute of Research Valdecilla (IDIVAL)","award":["INT24\/00060","CSI23\/24"],"award-info":[{"award-number":["INT24\/00060","CSI23\/24"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JCM"],"abstract":"<jats:p>Background: Although Presenilin-1 (PSEN1) mutations are classically associated with early-onset Alzheimer\u2019s disease (AD), spastic paraparesis (SP) may occasionally represent as an initial or even isolated clinical manifestation. Methods: We report the novel association of a PSEN1 mutation (Leu282Arg) with isolated SP at onset in a patient with a family history of early-onset AD. Additionally, we reviewed previously published cases describing similar presentations related to PSEN1 mutations. Results: The age of reported patients ranged from 24 to 60 years. The most common clinical course included the presence of cotton wool plaques and a progressive development of cognitive decline following the onset of SP. A positive family history of either motor or cognitive symptoms was consistently observed. Conclusions: Our findings emphasize the clinical importance of considering PSEN1 mutations in the differential diagnosis of patients presenting with spastic paraparesis, particularly in the presence of cognitive symptoms, cerebral amyloid angiopathy, or a family history of AD.<\/jats:p>","DOI":"10.3390\/jcm14176150","type":"journal-article","created":{"date-parts":[[2025,9,2]],"date-time":"2025-09-02T13:01:13Z","timestamp":1756818073000},"page":"6150","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Novel Association of the Presenilin-1 (Leu282Arg) Mutation with Isolated Spastic Paraparesis: Case Presentation and Review of Current Evidence"],"prefix":"10.3390","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0009-0008-5675-9557","authenticated-orcid":false,"given":"Mar\u00eda","family":"De la Sen-Dom\u00ednguez","sequence":"first","affiliation":[{"name":"Service of Neurology, University Hospital de Valdecilla-IDIVAL, 39011 Santander, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Manuel","family":"Delgado-Alvarado","sequence":"additional","affiliation":[{"name":"Service of Neurology, Hospital General Sierrallana-IDIVAL, 39300 Torrelavega, Spain"},{"name":"Centro de Investigaci\u00f3n en Red Enfermedades Neurodegenerativas (CIBERNED), 28029 Madrid, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marta","family":"Torres-Barquin","sequence":"additional","affiliation":[{"name":"Service of Radiology, Hospital General Sierrallana-IDIVAL, 39300 Torrelavega, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Remedios","family":"Quirce","sequence":"additional","affiliation":[{"name":"Service of Nuclear Medicine, University Hospital de Valdecilla-IDIVAL, 39011 Santander, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7929-1055","authenticated-orcid":false,"given":"Javier","family":"Riancho","sequence":"additional","affiliation":[{"name":"Service of Neurology, Hospital General Sierrallana-IDIVAL, 39300 Torrelavega, Spain"},{"name":"Centro de Investigaci\u00f3n en Red Enfermedades Neurodegenerativas (CIBERNED), 28029 Madrid, Spain"},{"name":"Department of Medicine and Psychiatry, University of Cantabria, 39005 Santander, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,8,30]]},"reference":[{"key":"ref_1","first-page":"249","article-title":"Sur les formes familiales precoces de la maladie d\u2019Alzheimer","volume":"102","author":"Maere","year":"1940","journal-title":"Monatschr. 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