{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,26]],"date-time":"2026-06-26T11:52:16Z","timestamp":1782474736965,"version":"3.54.5"},"reference-count":72,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2025,6,5]],"date-time":"2025-06-05T00:00:00Z","timestamp":1749081600000},"content-version":"vor","delay-in-days":4,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Journal of Neurochemistry"],"published-print":{"date-parts":[[2025,6]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Alzheimer's disease (AD) involves cognitive decline, possibly via multiple concurrent pathologies associated with iron accumulation. To investigate if iron accumulation in AD is more likely due to pathological iron\u2010rich compartments, or a compensatory response of iron within oligodendrocytes to disease progression, we sought to quantify iron\u2010rich staining (via Perl's diaminobenzidine; DAB). Healthy wild\u2010type (WT) and APP\n                    <jats:sup>Swe<\/jats:sup>\n                    \u2010PS1\u0394e9 (APP\u2010PS1; amyloid\u2010beta overexpressing) male mice were examined during middle age, at 14\u2009months. The frontal cortex, a brain region affected over the course of dementia progression, was investigated. Iron\u2010rich compartments were found across genotypes, including oligodendrocytes and immune cells at the blood\u2013brain barrier, and exclusively amyloid plaques in the APP\u2010PS1 genotype. A semi\u2010automated approach was employed to quantify the staining intensity of iron\u2010rich compartments with light microscopy. Mouse frontal cortex of each genotype was also assessed qualitatively and ultrastructurally with scanning electron microscopy, to novelly discern and confirm iron\u2010rich staining (via Perl's DAB). We found parenchymal iron staining corresponding to oligodendrocytes, pericytes, astrocytes, microglia and\/or infiltrating macrophages, and amyloid plaques; increased iron deposition and clustering were detected in middle\u2010aged male APP\u2010PS1 versus WT frontal cortex, supporting that AD pathology may involve greater brain iron levels and local clustering. Unexpectedly, iron\u2010rich cells were enriched at the central nervous system (CNS) interface and perivascular space in control and APP\u2010PS1 mouse models, with ultrastructural examination revealing examples of these cells loaded with many secretory granules containing iron. Together, our results provide novel exploration and confirmation of iron\u2010rich cells\/compartments in scanning electron microscopy and reinforce literature that iron deposition is relatively increased in AD over healthy cognitive aging and involves greater local clusters of iron burden. Increased iron burden along the aging trajectory, regardless of cognitive status, may also be attributed to novelly discovered iron\u2010rich cells secreting granules along the CNS border.\n                    <jats:boxed-text content-type=\"graphic\" position=\"anchor\">\n                      <jats:graphic xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" mimetype=\"image\/png\" position=\"anchor\" specific-use=\"enlarged-web-image\" xlink:href=\"graphic\/jnc70086-fig-0010-m.png\">\n                        <jats:alt-text>image<\/jats:alt-text>\n                      <\/jats:graphic>\n                    <\/jats:boxed-text>\n                  <\/jats:p>","DOI":"10.1111\/jnc.70086","type":"journal-article","created":{"date-parts":[[2025,6,5]],"date-time":"2025-06-05T05:00:44Z","timestamp":1749099644000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Exploring Iron Deposition Patterns Using Light and Electron Microscopy in the Mouse Brain Across Aging and Alzheimer's Disease Pathology Conditions"],"prefix":"10.1111","volume":"169","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1147-2073","authenticated-orcid":false,"given":"Victor","family":"Lau","sequence":"first","affiliation":[{"name":"Division of Medical Sciences University of Victoria  Victoria British Columbia Canada"},{"name":"Institute on Aging and Lifelong Health (IALH) University of Victoria  Victoria British Columbia Canada"},{"name":"Centre for Advanced Materials and Related Technology (CAMTEC) University of Victoria  Victoria British Columbia Canada"},{"name":"Neuroscience Graduate Program University of Victoria  Victoria British Columbia Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1546-0304","authenticated-orcid":false,"given":"Jared","family":"VanderZwaag","sequence":"additional","affiliation":[{"name":"Division of Medical Sciences University of Victoria  Victoria British Columbia Canada"},{"name":"Centre for Advanced Materials and Related Technology (CAMTEC) University of Victoria  Victoria British Columbia Canada"},{"name":"Neuroscience Graduate Program University of Victoria  Victoria British Columbia Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-2307-3460","authenticated-orcid":false,"given":"Colin J.","family":"Murray","sequence":"additional","affiliation":[{"name":"Division of Medical Sciences University of Victoria  Victoria British Columbia Canada"},{"name":"Institute on Aging and Lifelong Health (IALH) University of Victoria  Victoria British Columbia Canada"},{"name":"Centre for Advanced Materials and Related Technology (CAMTEC) University of Victoria  Victoria British Columbia Canada"},{"name":"Neuroscience Graduate Program University of Victoria  Victoria British Columbia 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