PDIA3 Expression Is Altered in the Limbic Brain Regions of Triple-Transgenic Mouse Model of Alzheimer's Disease

In the present study, we used a mouse model of Alzheimer's disease (AD) (3xTg-AD mice) to longitudinally analyse the expression level of PDIA3, a protein disulfide isomerase and endoplasmic reticulum (ER) chaperone, in selected brain limbic areas strongly affected by AD-pathology (amygdala, entorhinal cortex, dorsal and ventral hippocampus). Our results suggest that, while in Non-Tg mice PDIA3 levels gradually reduce with aging in all brain regions analyzed, 3xTg-AD mice showed an age-dependent increase in PDIA3 levels in the amygdala, entorhinal cortex, and ventral hippocampus. A significant reduction of PDIA3 was observed in 3xTg-AD mice already at 6 months of age, as compared to age-matched Non-Tg mice. A comparative immunohistochemistry analysis performed on 3xTg-AD mice at 6 (mild AD-like pathology) and 18 (severe AD-like pathology) months of age showed a direct correlation between the cellular level of A beta and PDIA3 proteins in all the brain regions analysed, even if with different magnitudes. Additionally, an immunohistochemistry analysis showed the presence of PDIA3 in all post-mitotic neurons and astrocytes. Overall, altered PDIA3 levels appear to be age- and/or pathology-dependent, corroborating the ER chaperone's involvement in AD pathology, and supporting the PDIA3 protein as a potential novel therapeutic target for the treatment of AD.

Automated summary

In this study, a mouse model of Alzheimer's disease (AD) was used to investigate the expression of PDIA3, an endoplasmic reticulum chaperone, in brain regions affected by AD pathology. The results showed an age-dependent increase in PDIA3 levels in AD mice, and a significant reduction in PDIA3 at an early age compared to non-AD mice. Immunohistochemistry analysis revealed a correlation between the levels of A beta and PDIA3 proteins in all brain regions analyzed. The findings suggest that altered PDIA3 levels may play a role in AD pathology and could be a potential therapeutic target.