Dementia with Lewy Bodies (DLB) is caused by aggregation of insoluble α-synuclein (α-syn) in neurons and patients exhibit cognitive impairment involving the anterior cingulate cortex (ACC). Parvalbumin-expressing interneurons (PVIs) are critical for normal cognitive function and are often surrounded by a specialised extracellular matrix, the perineuronal nets (PNNs). Loss of PVIs and PNNs occurs in Alzheimer’s disease but their role in DLB remains unclear. In addition, neuroinflammatory changes may also play an early role in DLB. Using transgenic mice expressing human mutant α-syn (hA30P), we investigated the impact of α-syn pathology on PVIs, PNNs, microglia and astrocytes in the ACC in young and aged A30P and control (wild-type) mice. Immunofluorescence was conducted against PV for PVI detection, lectin-avidin for PNNs, Iba-1 for microglia and GFAP for reactive astrocytes in coronal sections of frontal cortex. Sections were imaged using confocal microscopy and densitometric analysis was conducted.We compared the expression and co-localisation of PVIs with PNNs and α-syn and glial cell expression in the ACC. In young and aged A30P mice, there was a trend towards a decrease in PVI number. Interestingly, we found a significantly greater proportion of PNNs surrounding non-PV cells in young A30P animals. In all aged animals, we also found a significant increase in the %area of GFAP+ astrocytes.A shift in PNN localisation to potentially surround pyramidal neurons in A30P mice, might be protective against α-syn pathology. Additionally, our data suggests increased neuroinflammation is correlated with age in the ACC in hA30P and control mice.