Spatial and spectral mapping of traffic-related air pollution (TRAP) nanoparticles in relation to plaques and inflammatory markers in an Alzheimer disease model

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This paper investigated how chronic exposure to traffic-related air pollution (TRAP) affects deposition, composition, and spatial relationships of ultrafine particulate matter (UFPM) in the hippocampus of TgF344-AD rats, using enhanced darkfield hyperspectral imaging combined with confocal immunofluorescence for microglial markers (CD68/Iba1) and amyloid beta (Aβ) plaques. UFPM accumulation was higher in TRAP-exposed females, and particles located near plaques showed red-shifted spectral signatures consistent with biochemical transformation, with clustering of particle spectra by TRAP exposure and plaque proximity. UFPM was rarely observed within plaques or microglia, leading the authors to conclude that effects may occur via indirect neuroimmune modulation rather than direct localization in those structures. The study’s key caveat is that the work is performed in a rodent Alzheimer disease model, limiting direct translation to human disease. The paper does not explicitly discuss endometriosis or adenomyosis; it was included in the corpus via a keyword match in the upstream search index.

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Abstract

Chronic exposure to traffic-related air pollution (TRAP) is linked to increased risk of neurodegenerative diseases, including Alzheimer disease (AD). Ultrafine particulate matter (UFPM) is a suspected driver of TRAP neurotoxicity, but its spatial interactions with AD pathology remain poorly defined. We investigated the distribution, composition, and pathological context of TRAP-derived UFPM in the hippocampus of TgF344-AD rats chronically exposed to TRAP or filtered air (FA) for 14 months. Using a multimodal imaging workflow that combines enhanced darkfield hyperspectral imaging (EDF-HSI) with confocal immunofluorescence for microglia (CD68/Iba1) and amyloid beta (Aβ) plaques (Thioflavin S), we mapped the localization and spectral properties of UFPM in situ. UFPM accumulation was elevated in TRAP-exposed females, suggesting sex-specific vulnerability in blood-brain barrier (BBB) permeability or particle retention. Particles near plaques showed red-shifted spectral signatures, consistent with biochemical transformation. Dimension reduction revealed clustering of particle spectra by TRAP exposure and plaque proximity. However, UFPM was rarely found within plaques or microglia, implying indirect neuroimmune modulation. These findings highlight a novel spatial and spectral imaging approach for characterizing environmental nanoparticle interactions in the brain and suggest that chronic TRAP exposure may influence AD-related inflammation and pathology in a sex- and region-dependent manner.
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Abstract Chronic exposure to traffic-related air pollution (TRAP) is linked to increased risk of neurodegenerative diseases, including Alzheimer disease (AD). Ultrafine particulate matter (UFPM) is a suspected driver of TRAP neurotoxicity, but its spatial interactions with AD pathology remain poorly defined. We investigated the distribution, composition, and pathological context of TRAP-derived UFPM in the hippocampus of TgF344-AD rats chronically exposed to TRAP or filtered air (FA) for 14 months. Using a multimodal imaging workflow that combines enhanced darkfield hyperspectral imaging (EDF-HSI) with confocal immunofluorescence for microglia (CD68/Iba1) and amyloid beta (Aβ) plaques (Thioflavin S), we mapped the localization and spectral properties of UFPM in situ. UFPM accumulation was elevated in TRAP-exposed females, suggesting sex-specific vulnerability in blood-brain barrier (BBB) permeability or particle retention. Particles near plaques showed red-shifted spectral signatures, consistent with biochemical transformation. Dimension reduction revealed clustering of particle spectra by TRAP exposure and plaque proximity. However, UFPM was rarely found within plaques or microglia, implying indirect neuroimmune modulation. These findings highlight a novel spatial and spectral imaging approach for characterizing environmental nanoparticle interactions in the brain and suggest that chronic TRAP exposure may influence AD-related inflammation and pathology in a sex-and region-dependent manner. Synopsis This study shows that chronic traffic-related air pollution alters ultrafine particulate matter deposition and neuroinflammation in a rodent Alzheimer model, revealing region- and sex-specific vulnerability in the brain’s response to environmental exposure. Competing Interest Statement The authors have declared no competing interest.

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