Alzheimer's disease (AD) is the most prevalent form of dementia, characterized by a progressive decline in cognitive function that ultimately leads to mortality. Timely detection, particularly during the early-stage of mild-cognitive-impairment (MCI) is crucial for effective intervention. Converging evidence showed that parvalbumin-interneurons (PVI) cortical microcircuitry play an important role for normal cognitive functions. PVI are highly sensitive to oxidative stress (OS) and mitochondrial impairment, conditions that are well known to increase with ageing. Therefore, there is a critical need for biomarkers allowing the early-stage detection of these impairments. We aim to study the dysregulation of the mitochondrial network in PVI and the associated OS in AD and MCI. Using formalin-fixed, paraffin-embedded postmortem-brain-tissue from AD and MCI patients and their age-matched healthy-controls (CTRL), we performed immunohistochemical-analyses on consecutive 12μm-sections to study PVI, OS and mitochondrial markers. Our preliminary findings revealed an increase of 8-OXO-DG staining, a marker of DNA oxidation, in AD group compared to MILD and CTRL. This increase is positively correlated with elevated PRX SO3 levels indicating an overoxidation of the antioxidant enzyme peroxiredoxin. No differences in PRX SO3 staining between groups. Additionally, differences in VDAC and HSP70 staining, markers for mitophagy, between groups suggest evolving mitochondrial dysfunction with disease progression. Furthermore, while PV-positive-cell count remained unchanged, a reduction in cell volume was observed, aligning with known brain atrophy in AD. Our findings shed light on the intricate interplay between OS, mitochondrial dysfunction, and PVI impairment in AD and MCI. Continued exploration is needed to refine early diagnostic biomarkers.