Traffic-related air pollution (TRAP) is associated with lower cognition and reduced white matter volume in older adults, specifically for particulate matter < 2.5-mu m diameter (PM2.5). Rodents exposed to TRAP have shown microglial activation and neuronal atrophy. We further investigated age differences of TRAP exposure, with focus on hippocampus for neuritic atrophy, white matter degeneration, and microglial activation. Young-and middle-aged mice (3 and 18 months female C57BL/6J) were exposed to nanoscalePM (nPM, < 0.2 mm diameter). Young mice showed selective changes in the hippocampal CA1 region, with neurite atrophy (-25%), decreased MBP (- 50%), and increased Iba1 (-50%), with dentate gyrus relatively unaffected. Exposure to nPM of young mice decreased GluA1 protein (- 40%) and increased TNFa mRNA (10 x). Older controls had age changes approximating nPM effects on young, with no response to nPM, suggesting an age-ceiling effect. The CA1 selective vulnerability in young mice parallels CA1 vulnerability in Alzheimer's disease. We propose that TRAP-associated human cognitive and white matter changes involve hippocampal responses to nPM that begin at younger ages. (C) 2017 Elsevier Inc. All rights reserved.