"Evaluation of neprilysin activity in Adipose-Derived stem cells from Alzheimer's disease patients"

Abstract

Introduction: The antibody drugs targeting β-amyloid in Alzheimer's disease pose risks of inflammation and vascular damage. It is known that neprilysin, an endogenous enzyme responsible for β-amyloid degradation, is reduced in areas with β-amyloid deposition. Supplementation of neprilysin could potentially contribute to Alzheimer's disease treatment. When considering the use of adipose tissue-derived stem cells (ADSCs) for Alzheimer's disease therapy, it is crucial to ensure that Alzheimer's disease patient-derived ADSCs maintain neprilysin activity. If so, the use of autologous ADSCs may lead to a treatment with minimal risks of rejection or infection. Therefore, we investigated the neprilysin activity in Alzheimer's disease patient-derived adipose tissue-derived stem cells to assess their potential in Alzheimer's disease treatment.

Methods: Five Alzheimer's disease patients (MSC1-5) and two Chronic Obstructive Pulmonary Disease (COPD) patients (MSC6-7) were enrolled. ADSCs were cultured for 6 days with varying seeding densities. On the 3rd day, the medium was replaced, and on the 6th day, ADSCs were harvested. Cells were stained for PE-Cy7 Mouse IgG1 κ Isotype control and PE-Cy Mouse Anti-Human CD10, and CD10 expression was assessed by flow cytometry. Ethical approval and informed consent were obtained.

Results: Neprilysin activity, crucial for β-amyloid degradation, was assessed in ADSCs. Positivity rates for CD10 expression in ADSCs from Alzheimer's patients were consistently high: 99.6%, 99.5%, 99.9%, 99.3%, 99.8%, and 100.0%. Control ADSCs from COPD patients (MSC6-7) exhibited comparable positivity rates. Flow cytometry plots for all seven cases are presented in Figures 1-7.

Discussion: This study confirms the presence and maintenance of neprilysin activity in ADSCs from Alzheimer's disease patients. The high positivity rates for CD10 expression in these cells suggest that neprilysin, a key enzyme in β-amyloid degradation, remains active. The implications are significant, as ADSCs offer immune-compatible and low infection risk advantages. The study underscores the potential of autologous ADSCs as a therapeutic approach in Alzheimer's disease. Their ability to naturally harbor neprilysin activity, coupled with their safety profile, makes them a promising candidate for further exploration. While acknowledging the need for larger, more diverse cohorts and long-term studies, these findings contribute to the growing body of evidence supporting the development of stem cell-based interventions in Alzheimer's disease treatment.

Keywords: Adipose-derived stem cells; Alzheimer's disease; Amyloid β; Neprilysin; Therapeutic Potential.