Neutrophil-specific overexpression of angiotensin-converting enzyme in 3xTg-AD mice significantly reduced amyloid-beta plaque areas and improved spatial cognition compared to control AD mice.
Does genetic overexpression of ACE in neutrophils improve cognitive decline and reduce Aβ pathology in a mouse model of Alzheimer's disease?
Overexpressing ACE in neutrophils enhances Aβ clearance and reduces Alzheimer's-like cognitive decline in a mouse model, suggesting a potential therapeutic approach.
p-value: p=<0.05
Angiotensin-converting enzyme (ACE), a dipeptidyl carboxypeptidase, is known to cleave amyloid-beta (Aβ), and its reduced activity has been linked to the progression of Alzheimer’s disease (AD). Our research indicates that ACE is vital for myeloid cell functions. Using ACE10/10 recombinant mice, we demonstrated that overexpressing ACE in macrophages mitigates AD pathology in these mice. Given that neutrophils are the most abundant white blood cells, this study investigates whether ACE overexpression in neutrophils influences AD progression. We crossed NeuACE mice, which overexpress ACE in neutrophils, with 3xTg-AD mice to create AD-NeuACE mice. Behavioral changes and brain pathology were assessed through various behavioral mazes and histological assays. AD-NeuACE mice demonstrated improved cognitive functions and lower Aβ levels in the cortex and hippocampus compared to AD mice. In-vitro data indicate that ACE-overexpressing neutrophils are significantly more effective at phagocytosing and clearing Aβ fluorescence particles. This study suggests that overexpressing ACE in neutrophils could be a promising approach to managing AD-like phenotypes.
Shibata et al. (Mon,) conducted a other in Alzheimer's disease. Neutrophil-specific ACE overexpression (NeuACE) vs. Wild-type ACE 3xTg-AD mice (AD mice) was evaluated on Cognitive function (Barnes maze performance) and Aβ plaque area (p=<0.05). Neutrophil-specific overexpression of angiotensin-converting enzyme in 3xTg-AD mice significantly reduced amyloid-beta plaque areas and improved spatial cognition compared to control AD mice.