ABSTRACT
Alzheimer's disease (AD) is the commonest neurodegenerative disease and, in recent years, studies have increasingly shown that vascular lesions are involved in the pathology of AD onset and progression. Many vascular changes precede the pathological changes and clinical symptoms of AD, and vascular lesions and AD have many common risk factors. Understanding the relationship between vascular factors and the pathological process of AD may help us to identify novel prevention and treatment strategies as well as delay disease progress. Previous studies have shown that lycopene has neuroprotective, antioxidant, and anticancer effects; however, the specific molecular mechanism mediating these effects remains unknown. In the present study, we found: 1) lycopene improved learning and memory in an AD mouse model; 2) lycopene inhibited amyloid plaque aggregation and neuroinflammation; and 3) lycopene induced LXR expression and activated the LXR-PI3K-AKT signaling pathway. Our findings suggest that promotion of neurogenesis and improvement of the functions of the neurovascular unit could be a novel direction for the development of AD therapies.
Subject(s)
Alzheimer Disease/metabolism , Liver X Receptors/genetics , Liver X Receptors/metabolism , Lycopene/pharmacology , Phosphatidylinositol 3-Kinases/metabolism , Proto-Oncogene Proteins c-akt/metabolism , Vascular Remodeling/drug effects , Amyloid beta-Peptides/metabolism , Animals , Disease Models, Animal , Down-Regulation/drug effects , Memory/drug effects , Mice , Mice, Inbred C57BL , Morris Water Maze Test/drug effects , Plaque, Amyloid/metabolism , Signal TransductionABSTRACT
To address inconsistency as well as investigate the relationship between glaucoma and the risk of Alzheimer's disease (AD). We systematically conducted this meta-analysis based on observational studies published up to 15 January 2018, identified from PubMed and Web of Science. Two team members independently extracted the data and assessed the quality of each included study. Summary relative risk (RR) and 95% confidence intervals (CIs) were calculated using a random-effects model. Eight observational studies with 6870 AD cases were included. The majority of these studies (n = 6) were graded as low risk according to the Newcastle-Ottawa Quality Assessment Scale. Individuals diagnosed with glaucoma, compared to those who were not, had an increased risk of AD (RR = 1.52; 95% CI: 1.41-1.63; I2 = 97%, p < 0.001). A significant finding was also observed for primary open-angle glaucoma (RR = 1.52; 95% CI: 1.41-1.63; I2 = 97%, p < 0.001). However, when stratified by study design, only the case-control studies (RR = 1.08; 95% CI: 0.89-1.31; I2 = 37.3%, p = 0.207) yielded significant results, while the cohort studies did not (RR = 1.08; 95% CI: 0.89-1.31; I2 = 97.7%, p < 0.001). Of note, our meta-regression analysis suggested that study design might be a source of heterogeneity (p = 0.009). Additionally, a significantly positive association was observed when the analyses were restricted to Asia (RR = 2.03; 95% CI: 1.02-4.07). There was no significant publication bias in these analyses. Recent evidence suggests that glaucoma may increase the risk of AD. Additional cohort studies are needed to confirm these findings and to have improved knowledge on the true nature of this association.