Combinatorial Treatment Effects in a Cell Culture Model of Alzheimer's Disease

Background: Alzheimer's disease (AD) is the leading cause of dementia, and as its prevalence increases, so does its detrimental impact on society. The currently available therapies have limited efficacy, leaving AD patients on an irrevocably fatal path of this disease. Objective: The purpose of this study was to test efficacy of a novel combinatorial treatment approach to alleviate AD-like pathology. Methods: We selected four naturally occurring compounds and used them in different combinations to test their effect on AD-like pathology. Employing a well-established cell culture AD model system, we evaluated levels of several diverse biomarkers associated with a number of cellular pathways associated with AD. The readouts included: amyloid-beta peptides, anti-inflammatory and anti-apoptotic proteins, oxidative enzymes, and reactive oxygen species. Results: Using this approach, we demonstrated that the compounds delivered in combination had higher efficacy than individual treatments. Specifically, we observed significant reduction in levels of the amyloid-beta peptides, as well as pro-inflammatory proteins and reactive oxygen species. Similarly, delivery of compounds in combination resulted in an increased expression of anti-apoptotic proteins and anti-oxidative enzymes. Collectively, these modifications in AD pathology biomarkers reflect a promising therapeutic and preventive strategy to combat this disease. Conclusion: The above findings support a novel therapeutic approach to address a currently unmet medical need, which would benefit not only AD patients and their caregivers, but also society as a whole.