Carbon monoxide and anti-amyloid-β combination therapy modulates miR-381 and molecular biomarkers in an aluminum chloride-induced rat model of Alzheimer's disease.

BACKGROUND

Alzheimer's disease (AD) involves intersecting amyloid, tau, oxidative stress, and apoptotic pathways.

OBJECTIVE

To determine whether combining controlled carbon monoxide (CO) exposure with anti-amyloid-β (Aβ) immunotherapy confers additive benefits on AD-relevant molecular and histological readouts in adult male Sprague-Dawley rats.

METHODS

Adult male Sprague-Dawley rats were assigned to one of five groups: Control, AD, CO, anti-Aβ, and a combination group (CO plus anti-Aβ), after induction of AD-like pathology with aluminum chloride (AlCl3). Outcomes included hippocampal Aβ, phosphorylated tau (p-tau), acetylcholinesterase (AChE), NRF2, and p53 (ELISA); hippocampal miR-381 expression (qRT-PCR); and hippocampal/cortical histology. Data were analyzed at the animal level using one-way ANOVA with post hoc tests.

RESULTS

CO and anti-Aβ monotherapies each reduced Aβ burden and tau phosphorylation versus the AD group. The combination produced the most significant shifts toward Control across Aβ, p-tau, AChE, NRF2, and p53, accompanied by significant upregulation of miR-381 and improved histopathology.

CONCLUSIONS

CO-mediated epigenetic/redox modulation and antibody-driven Aβ clearance act in complementary ways to mitigate AD-like pathology. These findings support epigenetic-immunologic combination strategies as a promising direction for preclinical AD therapy.