{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,26]],"date-time":"2026-10-26T18:32:49Z","timestamp":1793039569975,"version":"4.5.0"},"reference-count":73,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2025,4,28]],"date-time":"2025-04-28T00:00:00Z","timestamp":1745798400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Institute on Alcohol Abuse and Alcoholism","award":["AA-011431"],"award-info":[{"award-number":["AA-011431"]}]},{"name":"National Institute on Alcohol Abuse and Alcoholism","award":["AA-028408"],"award-info":[{"award-number":["AA-028408"]}]},{"name":"National Institute on Alcohol Abuse and Alcoholism","award":["AA-032106"],"award-info":[{"award-number":["AA-032106"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>The development of more effective disease-modifying treatments for Alzheimer\u2019s disease (AD) is compromised by the lack of streamlined measures to detect and monitor the full spectrum of neurodegeneration, including white matter pathology, which begins early. This study utilized an established intracerebral streptozotocin (STZ) model of AD to examine the potential utility of a non-invasive serum extracellular vesicle (SEV)-based liquid biopsy approach for detecting a broad range of molecular pathologies related to neurodegeneration. The design enabled comparative analysis of immunoreactivity in frontal lobe tissue (FLTX), frontal lobe-derived EVs (FLEVs), and SEVs. Long Evans rats were administered i.c. STZ or saline (control) on postnatal day 3 (P3). Morris Water Maze testing was performed from P24 to P27. On P31\u201332, the rats were sacrificed to harvest FLTX and serum for EV characterization. STZ caused brain atrophy, with deficits in spatial learning and memory. STZ significantly impacted FLEV and SEV nanoparticle abundance and size distributions and concordantly increased AD (Tau, pTau, and A\u03b2) and oxidative stress (ubiquitin, 4-HNE) biomarkers, as well as immunoreactivity to immature oligodendrocyte (PLP), non-myelinating glial (PDGFRA, GALC) proteins, MAG, nestin, and GFAP in FLTX and FLEV. The SEVs also exhibited concordant STZ-related effects, but they were limited to increased levels of 4-HNE, PLP, PDGFRA, GALC, MAG, and GFAP. The findings suggest that non-invasive EV-based liquid biopsy approaches could potentially be used to detect and monitor some aspects of AD-type neurodegeneration. Targeting brain-specific EVs in serum will likely increase the sensitivity of this promising non-invasive approach for diagnostic and clinical management.<\/jats:p>","DOI":"10.3390\/ijms26094190","type":"journal-article","created":{"date-parts":[[2025,4,29]],"date-time":"2025-04-29T07:49:36Z","timestamp":1745912976000},"page":"4190","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Comparative Brain and Serum Exosome Expression of Biomarkers in an Experimental Model of Alzheimer-Type Neurodegeneration: Potential Relevance to Liquid Biopsy Diagnostics"],"prefix":"10.3390","volume":"26","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5886-2306","authenticated-orcid":false,"given":"Suzanne M.","family":"de la Monte","sequence":"first","affiliation":[{"name":"Departments of Medicine, Pathology and Laboratory Medicine, Neurology, and Neurosurgery, Rhode Island Hospital, Women & Infants Hospital, Brown University Health, The Warren Alpert Medical School of Brown University, Providence, RI 02903, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-0069-2181","authenticated-orcid":false,"given":"Yiwen","family":"Yang","sequence":"additional","affiliation":[{"name":"Graduate Program in Biotechnology, Brown University, Providence, RI 02912, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anjali","family":"Prabhu","sequence":"additional","affiliation":[{"name":"Graduate Program in Biotechnology, Brown University, Providence, RI 02912, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5927-5832","authenticated-orcid":false,"given":"Ming","family":"Tong","sequence":"additional","affiliation":[{"name":"Department of Medicine, Rhode Island Hospital, Brown University Health, The Warren Alpert Medical School of Brown University, Providence, RI 02903, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,4,28]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"505","DOI":"10.1001\/jamaneurol.2013.5847","article-title":"Amyloid-beta and tau: The trigger and bullet in Alzheimer disease pathogenesis","volume":"71","author":"Bloom","year":"2014","journal-title":"JAMA Neurol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1301","DOI":"10.3233\/JAD-230555","article-title":"Malignant Brain Aging: The Formidable Link Between Dysregulated Signaling Through Mechanistic Target of Rapamycin Pathways and Alzheimer\u2019s Disease (Type 3 Diabetes)","volume":"95","year":"2023","journal-title":"J. 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