Natural Carotenoids as Neuroprotective Agents for Alzheimer's Disease: An Evidence-Based Comprehensive Review

Alzheimer's disease (AD) is a neurodegenerative disorder of an ever-increasing aging population with various pathological features such as β-amyloid (Aβ) aggregation, oxidative stress, an impaired cholinergic system, and neuroinflammation. Several therapeutic drugs have been introduced to slow the progression of AD by targeting the above-mentioned pathways. In addition, emerging evidence suggests that naturally occurring compounds have the potential to serve as adjuvant therapies to alleviate AD symptoms. Carotenoids, a group of natural pigments with antioxidative and anti-inflammatory properties, are proposed to be implicated in neuroprotection. To obtain a comprehensive picture of the effect of carotenoids on AD prevention and development, we critically reviewed and discussed recent evidence from in silico, in vitro, in vivo, and human studies in databases including PubMed, Web of Science, Google Scholar, and Cochrane (CENTRAL). After analyzing the existing evidence, we found that high-quality randomized controlled trials (RCTs) are lacking to explore the neuroprotective role of carotenoids in AD pathogenesis and symptoms, especially carotenoids with solid preclinical evidence such as astaxanthin, fucoxanthin, macular carotenoids, and crocin, in order to develop effective preventive dietary supplements for AD patients to ameliorate the symptoms. This review points out directions for future studies to advance the knowledge in this field.