Efficacy of Protein-Based Therapies in Modulating Pathology and Symptoms of Alzheimer’s Disease: A Systematic Review

Abstract

Introduction: Beta-amyloid plaques and tau neurofibrillary tangles disrupt brain function, leading to the progressive cognitive and functional decline characteristic of Alzheimer’s Disease (AD). Current treatments provide only symptomatic relief, failing to address the underlying pathology. Protein-based therapies, including monoclonal antibodies and recombinant protein vaccines, aim to target these pathological mechanisms by clearing beta-amyloid deposits and modulating tau activity. This review evaluates the efficacy of these therapies in improving cognitive and functional outcomes while exploring their limitations and potential. Methods: This systematic review was conducted following PRISMA guidelines and the Cochrane Handbook for Systematic Reviews of Interventions (version 6.3). A comprehensive search of PubMed, Scopus, and Web of Science was performed. Inclusion criteria focused on studies evaluating protein-based therapies targeting amyloid-beta or tau in Alzheimer’s Disease. Data on cognitive and functional outcomes, safety, and biomarkers were extracted and synthesized to identify trends and gaps in the evidence. Results: Eight studies involving 724 participants met the inclusion criteria. Monoclonal antibodies, such as aducanumab, reduced amyloid-beta plaques within 24–48 weeks, but cognitive improvements were inconsistent. Recombinant vaccines, like Lu AF20513, induced strong immune responses in 65–80% of patients, especially with immunostimulant patches. Biomarkers such as alpha-2-macroglobulin showed promise in monitoring treatment efficacy. Adverse events, including mild infusion reactions, were more frequent with antibody therapies, highlighting the need for further optimization. Conclusion: Protein-based therapies show potential in Alzheimer’s Disease treatment by targeting amyloid-beta plaques and tau pathology. Monoclonal antibodies and recombinant vaccines offer promising results in reducing pathological hallmarks and improving immune responses. However, cognitive and functional benefits remain inconsistent, and adverse events are common. Further research is necessary to optimize these therapies, validate biomarkers, and ensure broader clinical applicability.