Effect of statins on amyloidosis in the rodent models of Alzheimer's disease: Evidence from the preclinical meta-analysis

Abstract

Introduction: Previous studies have shown contrasting results in determining efficacy of statins against amyloid beta accumulation. The aim of this study was to assess the impact of statin in AD. Method: We searched PubMed and Embase for relevant preclinical studies. A meta-analysis of the statin's efficacy on amyloidosis and cognitive impairment was performed. Also, stratified analysis was performed on several covariates including the type of statin used, gender and age of rodents and duration of statin therapy, to account for the reported heterogeneity in the results obtained. The study protocol was registered in PROSPERO (CRD42018102557). Result: 17 studies including 22 comparisons, containing a sample size of 446 rodents, participated in the meta-analysis of statin's effect on overall Aβ deposition. Although the effect of statin on overall Aβ deposition was found to be protective (p < 0.00001) but as we categorized the efficacy of statin on different Aβ species (soluble and insoluble Aβ40/42) and Aβ plaque load, we found that significance in the protection decreased. A stratified meta-analysis demonstrated a significant role in the duration of statin supplements and rodent's age on the heterogeneity of the results. Statin administered to rodents for the longest duration (>6 months) and younger rodents (<6 months of age) demonstrated significant efficacy of statin on Aβ deposition. Conclusion: Statin showed reduction in Aβ level but stratified analysis revealed that this effect of statin was dependent on rodent's age and duration of the treatment.