{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,10]],"date-time":"2026-01-10T01:08:57Z","timestamp":1768007337154,"version":"3.49.0"},"reference-count":60,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2006,3,17]],"date-time":"2006-03-17T00:00:00Z","timestamp":1142553600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Aging Cell"],"published-print":{"date-parts":[[2006,4]]},"abstract":"<jats:title>Summary<\/jats:title><jats:p>Transgenic mice carrying mutant Cu\/Zn superoxide dismutase (SOD1) recapitulate the motor impairment of human amyotrophic lateral sclerosis (ALS). The amyloid\u2010\u03b2 (A\u03b2) peptide associated with Alzheimer's disease is neurotoxic. To investigate the potential role of A\u03b2 in ALS development, we generated a double transgenic mouse line that overexpresses SOD1<jats:sup>G93A<\/jats:sup> and amyloid precursor protein (APP)\u2010C100. The transgenic mouse C100.SOD1<jats:sup>G93A<\/jats:sup> overexpresses A\u03b2 and shows earlier onset of motor impairment but has the same lifespan as the single transgenic SOD1<jats:sup>G93A<\/jats:sup> mouse. To determine the mechanism associated with this early\u2010onset phenotype, we measured copper and zinc levels in brain and spinal cord and found both significantly elevated in the single and double transgenic mice compared with their littermate control mice. Increased glial fibrillary acidic protein and decreased APP levels in the spinal cord of C100.SOD1<jats:sup>G93A<\/jats:sup> mice compared with the SOD1<jats:sup>G93A<\/jats:sup> mice agree with the neuronal damage observed by immunohistochemical analysis. In the spinal cords of C100.SOD1<jats:sup>G93A<\/jats:sup> double transgenic mice, soluble A\u03b2 was elevated in mice at end\u2010stage disease compared with the pre\u2010symptomatic stage. Buffer\u2010insoluble SOD1 aggregates were significantly elevated in the pre\u2010symptomatic mice of C100.SOD1<jats:sup>G93A<\/jats:sup> compared with the age\u2010matched SOD1<jats:sup>G93A<\/jats:sup> mice, correlating with the earlier onset of motor impairment in the C100.SOD1<jats:sup>G93A<\/jats:sup> mice. This study supports abnormal SOD1 protein aggregation as the pathogenic mechanism in ALS, and implicates a potential role for A\u03b2 in the development of ALS by exacerbating SOD1<jats:sup>G93A<\/jats:sup> aggregation.<\/jats:p>","DOI":"10.1111\/j.1474-9726.2006.00200.x","type":"journal-article","created":{"date-parts":[[2006,3,17]],"date-time":"2006-03-17T11:21:26Z","timestamp":1142594486000},"page":"153-165","source":"Crossref","is-referenced-by-count":37,"title":["Overexpression of A\u03b2 is associated with acceleration of onset of motor impairment and superoxide dismutase 1 aggregation in an amyotrophic lateral sclerosis mouse model"],"prefix":"10.1111","volume":"5","author":[{"given":"Qiao\u2010Xin","family":"Li","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Su San","family":"Mok","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Katrina M.","family":"Laughton","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Catriona A.","family":"McLean","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Irene","family":"Volitakis","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Robert A.","family":"Cherny","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nam Sang","family":"Cheung","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anthony R.","family":"White","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Colin L.","family":"Masters","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2006,3,17]]},"reference":[{"key":"e_1_2_6_2_1","doi-asserted-by":"publisher","DOI":"10.1006\/exnr.2002.7912"},{"key":"e_1_2_6_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0165-0173(03)00174-7"},{"key":"e_1_2_6_4_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.91.17.8292"},{"key":"e_1_2_6_5_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.281.5384.1851"},{"key":"e_1_2_6_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.nbd.2005.01.012"},{"key":"e_1_2_6_7_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M414327200"},{"key":"e_1_2_6_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0304-3940(03)00237-4"},{"key":"e_1_2_6_9_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.4276-04.2005"},{"key":"e_1_2_6_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0002-9440(10)65220-0"},{"key":"e_1_2_6_11_1","first-page":"1271","article-title":"Development of central nervous system pathology in a murine transgenic model of human amyotrophic lateral sclerosis","volume":"145","author":"Dal Canto MC","year":"1994","journal-title":"Am. 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