{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,29]],"date-time":"2026-07-29T15:13:15Z","timestamp":1785337995730,"version":"3.55.0"},"reference-count":63,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2024,6,12]],"date-time":"2024-06-12T00:00:00Z","timestamp":1718150400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Alzheimer\u2019s disease (AD), the leading cause of dementia worldwide, remains a challenge due to its complex origin and degenerative character. The need for accurate biomarkers and treatment targets hinders early identification and intervention. To fill this gap, we used a novel longitudinal proteome methodology to examine the temporal development of molecular alterations in the cortex of an intracerebroventricular streptozotocin (ICV-STZ)-induced AD mouse model for disease initiation and progression at one, three-, and six-weeks post-treatment. Week 1 revealed metabolic protein downregulation, such as Aldoa and Pgk1. Week 3 showed increased Synapsin-1, and week 6 showed cytoskeletal protein alterations like Vimentin. The biological pathways, upstream regulators, and functional effects of proteome alterations were dissected using advanced bioinformatics methods, including Ingenuity Pathway Analysis (IPA) and machine learning algorithms. We identified Mitochondrial Dysfunction, Synaptic Vesicle Pathway, and Neuroinflammation Signaling as disease-causing pathways. Huntington\u2019s Disease Signaling and Synaptogenesis Signaling were stimulated while Glutamate Receptor and Calcium Signaling were repressed. IPA also found molecular connections between PPARGC1B and AGT, which are involved in myelination and possible neoplastic processes, and MTOR and AR, which imply mechanistic involvements beyond neurodegeneration. These results help us comprehend AD\u2019s molecular foundation and demonstrate the promise of focused proteomic techniques to uncover new biomarkers and therapeutic targets for AD, enabling personalized medicine.<\/jats:p>","DOI":"10.3390\/ijms25126469","type":"journal-article","created":{"date-parts":[[2024,6,12]],"date-time":"2024-06-12T06:47:30Z","timestamp":1718174850000},"page":"6469","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Deciphering Early and Progressive Molecular Signatures in Alzheimer\u2019s Disease through Integrated Longitudinal Proteomic and Pathway Analysis in a Rodent Model"],"prefix":"10.3390","volume":"25","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5112-9005","authenticated-orcid":false,"given":"Hamad","family":"Yadikar","sequence":"first","affiliation":[{"name":"Department of Biological Sciences, Faculty of Science, Kuwait University, Sabah AlSalem University City, Kuwait City 13060, Kuwait"},{"name":"OMICS Research Unit, Research Core Facility, Faculty of Medicine, Kuwait University, Kuwait City 13110, Kuwait"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mubeen A.","family":"Ansari","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Toxicology, Faculty of Medicine, Kuwait University, Kuwait City 13110, Kuwait"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8357-1252","authenticated-orcid":false,"given":"Mohamed","family":"Abu-Farha","sequence":"additional","affiliation":[{"name":"Department of Translational Research, Dasman Diabetes Institute, Kuwait City 15462, Kuwait"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shibu","family":"Joseph","sequence":"additional","affiliation":[{"name":"Department of Special Service Facility, Dasman Diabetes Institute, Kuwait City 15462, Kuwait"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Betty T.","family":"Thomas","sequence":"additional","affiliation":[{"name":"OMICS Research Unit, Research Core Facility, Faculty of Medicine, Kuwait University, Kuwait City 13110, Kuwait"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5409-3829","authenticated-orcid":false,"given":"Fahd","family":"Al-Mulla","sequence":"additional","affiliation":[{"name":"Department of Translational Research, Dasman Diabetes Institute, Kuwait City 15462, Kuwait"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,6,12]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"33","DOI":"10.1038\/s41572-021-00269-y","article-title":"Alzheimer disease","volume":"7","author":"Knopman","year":"2021","journal-title":"Nat. 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