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The current study is based on a global proteome analysis of brain samples from patients (\n                    <jats:italic>n<\/jats:italic>\n                    \u2009=\u200938) with rapidly progressive AD (rpAD\u2014survival time\u2009&lt;\u20093\u00a0years), sporadic AD (spAD\u2014survival time of 8\u201310\u00a0years), and healthy controls. Proteome analysis revealed a differential regulation of 79 proteins and highlighted the dysregulation of mitochondrial machinery and glucose metabolism in rpAD. Dihydrolipoamide dehydrogenase (DLDH), a mitochondrial oxidoreductase, showed a significant reduction and delocalization in rpAD. In vitro analysis revealed a potential role of DLDH in the aggregation of amyloid beta. Rapid progression in AD may be influenced by the energy homeostasis and redox dysfunction linked with the DLDH.\n                  <\/jats:p>","DOI":"10.1007\/s12035-025-05327-0","type":"journal-article","created":{"date-parts":[[2025,11,19]],"date-time":"2025-11-19T01:08:40Z","timestamp":1763514520000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Proteomic Profiling Reveals Mitochondrial Dysregulation in Rapidly Progressive Alzheimer\u2019s: Role of DLDH in Amyloid Beta Aggregation"],"prefix":"10.1007","volume":"63","author":[{"given":"Saima","family":"Zafar","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Aneeqa","family":"Noor","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Neelam","family":"Younas","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mohsin","family":"Shafiq","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kathrin","family":"Dittmar","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Oleksandr","family":"Yagensky","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Matthias","family":"Schmitz","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Isidre","family":"Ferrer","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Peter","family":"Hermann","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Inga","family":"Zerr","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2025,11,19]]},"reference":[{"key":"5327_CR1","unstructured":"Alzheimer\u2019s Association, 2023 Alzheimer\u2019s disease facts and figures. 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