Exploring iron deposition patterns using light and electron microscopy in the mouse brain across aging and Alzheimer's disease pathology conditions

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dc.contributor.authorLau, Victor
dc.contributor.authorVanderZwaag, Jared
dc.contributor.authorMurray, Colin J.
dc.contributor.authorTremblay, Marie-Ève
dc.date.accessioned2026-03-05T17:18:54Z
dc.date.available2026-03-05T17:18:54Z
dc.date.copyright2025
dc.description.abstractAlzheimer'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-rich compartments, or a compensatory response of iron within oligodendrocytes to disease progression, we sought to quantify iron-rich staining (via Perl's diaminobenzidine; DAB). Healthy wild-type (WT) and APPSwe-PS1?e9 (APP-PS1; amyloid-beta overexpressing) male mice were examined during middle age, at 14?months. The frontal cortex, a brain region affected over the course of dementia progression, was investigated. Iron-rich compartments were found across genotypes, including oligodendrocytes and immune cells at the blood-brain barrier, and exclusively amyloid plaques in the APP-PS1 genotype. A semi-automated approach was employed to quantify the staining intensity of iron-rich 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-rich 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-aged male APP-PS1 versus WT frontal cortex, supporting that AD pathology may involve greater brain iron levels and local clustering. Unexpectedly, iron-rich cells were enriched at the central nervous system (CNS) interface and perivascular space in control and APP-PS1 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-rich 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-rich cells secreting granules along the CNS border. See PDF for illustration in abstract.
dc.description.reviewstatusReviewed
dc.description.scholarlevelFaculty
dc.description.sponsorshipV.L., J.V., and C.J.M. are supported by graduate award scholarships from the Faculty of Graduate Studies, University of Victoria. C.J.M. is also supported by a Branch Out Neurological Foundation Graduate Grant. J.V. is supported by a Canadian Institute for Health Research doctoral funding. M.E.T. is a Tier II Canada Research Chair in Neurobiology of Aging and Cognition. Finally, EM images were generated via a Crossbeam 350 scanning electron microscope acquired with funding from a Canada Foundation for Innovation John R. Evans Leaders Fund grant (#39965 Laboratory of ultrastructural insights into the neurobiology of aging and cognition). Funding was also obtained from a start-up grant received from the University of Victoria's Division of Medical Sciences.
dc.identifier.citationLau, V., VanderZwaag, J., Murray, C. J., & Tremblay, M. (2025). Exploring iron deposition patterns using light and electron microscopy in the mouse brain across aging and Alzheimer's disease pathology conditions. Journal of Neurochemistry, 169(6), e70086. https://doi.org/10.1111/jnc.70086
dc.identifier.urihttps://doi.org/10.1111/jnc.70086
dc.identifier.urihttps://hdl.handle.net/1828/23411
dc.language.isoen
dc.publisherJournal of Neurochemistry
dc.rightsCC BY-NC-ND 4.0en
dc.rights.urihttps://creativecommons.org/licenses/by-nc-nd/4.0/
dc.subjectAlzheimer's disease
dc.subjectamyloid plaques
dc.subjectCNS border-associated cells
dc.subjectelectron microscopy
dc.subjectiron deposition
dc.subjectmicroglia
dc.subjectInstitute on Aging and Lifelong Health
dc.subjectCentre for Advanced Materials and Related Technology (CAMTEC)
dc.subject.departmentDivision of Medical Sciences
dc.subject.departmentSchool of Medical Sciences
dc.titleExploring iron deposition patterns using light and electron microscopy in the mouse brain across aging and Alzheimer's disease pathology conditions
dc.typeArticle

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