Isoform-Dependent Effects of Apolipoprotein E on Sphingolipid Metabolism in Neural Cells

2021 ◽  
pp. 1-16
Author(s):  
Makoto Kurano ◽  
Kazuhisa Tsukamoto ◽  
Eri Sakai ◽  
Masumi Hara ◽  
Yutaka Yatomi
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Apolipoprotein E ◽  
Sphingolipid Metabolism ◽  
Neural Cells ◽  
Protective Effects ◽  
Apoe Isoforms ◽  
Potential Association ◽  
Sphingosine 1 Phosphate ◽  
U251 Cells

Background: Sphingosine 1-phosphate (S1P) and ceramides have been implicated in the development of Alzheimer’s disease. Apolipoprotein E (ApoE) isoforms are also involved in the development of Alzheimer’s disease. Objective: We aimed at elucidating the potential association of the ApoE isoforms with sphingolipid metabolism in the central nervous system. Methods: We investigated the modulations of apolipoprotein M (apoM), a carrier of S1P, S1P, and ceramides in Apoeshl mice, which spontaneously lack apoE, and U251 cells and SH-SY5Y cells infected with adenovirus vectors encoding for apoE2, apoE3, and apoE4. Results: In the brains of Apoeshl mice, the levels of apoM were lower, while those of ceramides were higher. In U251 cells, cellular apoM and S1P levels were the highest in the cells overexpressing apoE2 among the apoE isoforms. The cellular and medium contents of ceramides decreased in the order of the cells overexpressing apoE3 > apoE2 and increased in the cells overexpressing apoE4. In SH-SY5Y cells, apoM mRNA and medium S1P levels were also the highest in the cells overexpressing apoE2. The cellular contents of ceramides decreased in the order of the cells overexpressing apoE3 > apoE2 = apoE4 and those in medium decreased in the order of the cells overexpressing apoE3 > apoE2, while increased in the cells overexpressing apoE4. Conclusion: The modulation of apoM and S1P might partly explain the protective effects of apoE2 against Alzheimer’s disease, and the modulation of ceramides might be one of the mechanisms explaining the association of apoE4 with the development of Alzheimer’s disease.

scholarly journals APOE2 is associated with longevity independent of Alzheimer’s disease

eLife ◽  
2020 ◽  
Vol 9 ◽  
Author(s):  
Mitsuru Shinohara ◽  
Takahisa Kanekiyo ◽  
Masaya Tachibana ◽  
Aishe Kurti ◽  
Motoko Shinohara ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Lipid Metabolism ◽  
Animal Models ◽  
Apolipoprotein E ◽  
Activity Levels ◽  
Protective Effects ◽  
Observable Feature

Although the ε2 allele of apolipoprotein E (APOE2) benefits longevity, its mechanism is not understood. The protective effects of the APOE2 on Alzheimer’s disease (AD) risk, particularly through their effects on amyloid or tau accumulation, may confound APOE2 effects on longevity. Herein, we showed that the association between APOE2 and longer lifespan persisted irrespective of AD status, including its neuropathology, by analyzing clinical datasets as well as animal models. Notably, APOE2 was associated with preserved activity during aging, which also associated with lifespan. In animal models, distinct apoE isoform levels, where APOE2 has the highest, were correlated with activity levels, while some forms of cholesterol and triglycerides were associated with apoE and activity levels. These results indicate that APOE2 can contribute to longevity independent of AD. Preserved activity would be an early-observable feature of APOE2-mediated longevity, where higher levels of apoE2 and its-associated lipid metabolism might be involved.

P4-068: CLINICAL RELEVANCE OF APOE GENOTYPING AND APOLIPOPROTEIN E-ɛ4 IMMUNOASSAYS IN ALZHEIMER'S DISEASE

2014 ◽  
Vol 10 ◽  
pp. P808-P808
Author(s):  
Femke Soetewey ◽  
Hanne Struyfs ◽  
Erik Stoops ◽  
Christine Van Broeckhoven ◽  
Hugo Vanderstichele ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Apolipoprotein E ◽  
Clinical Relevance

The Associations of Plasma/Serum Carotenoids with Alzheimer’s Disease: A Systematic Review and Meta-Analysis

2021 ◽  
pp. 1-12
Author(s):  
Mingyue Qu ◽  
Hanxu Shi ◽  
Kai Wang ◽  
Xinggang Wang ◽  
Nan Yu ◽  
...  
Keyword(s):  
Systematic Review ◽  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Meta Analysis ◽  
Scoring Systems ◽  
Serum Levels ◽  
Epidemiological Studies ◽  
Pooled Analysis ◽  
Protective Effects ◽  
Mean Differences

Background: Multiple lines of evidence indicate protective effects of carotenoids in Alzheimer’s disease (AD). However, previous epidemiological studies reported inconsistent results regarding the associations between carotenoids levels and the risk of AD. Objective: Our study aims to evaluate the associations of six major members of carotenoids with the occurrence of AD by conducting a systematic review and meta-analysis. Methods: Following PRISMA guidelines, a comprehensive literature search of PubMed, Web of Science, Ebsco, and PsycINFO databases was conducted, and the quality of each included studies was evaluated by a validated scoring systems. Standardized mean differences (SMD) with 95%confidence intervals (CI) were determined by using a random effects model. Heterogeneity was evaluated by I2 statistics. Publication bias was detected using funnel plots and Egger’s test. Results: Sixteen studies, with 10,633 participants were included. Pooled analysis showed significantly lower plasma/serum levels of lutein (SMD = –0.86, 95%CI: –1.67 to –0.05, p = 0.04) and zeaxanthin (SMD = –0.59; 95%CI: –1.12 to –0.06, p = 0.03) in patients with AD versus cognitively intact controls, while α-carotene (SMD = 0.21, 95%CI: –0.68 to 0.26, p = 0.39), β-carotene (SMD = 0.04, 95%CI: –0.57 to 0.65, p = 0.9), lycopene (SMD = –0.12, 95%CI: –0.96 to 0.72, p = 0.78), and β-cryptoxanthin (SMD = –0.09, 95%CI: –0.83 to 0.65, p = 0.81) did not achieve significant differences. Conclusion: Of six major members of carotenoids, only lutein and zeaxanthin concentrations in plasma/serum were inversely related to the risk of AD. More high-quality longitudinal studies are needed to verify these findings.

scholarly journals Apolipoprotein E ε4 Allele Is Unrelated to Cognitive or Functional Decline in Alzheimer’s Disease: Retrospective and Prospective Analysis

2006 ◽  
Vol 22 (1) ◽  
pp. 73-82 ◽  
Author(s):  
Timothy Kleiman ◽  
Kristina Zdanys ◽  
Benjamin Black ◽  
Tracy Rightmer ◽  
Monique Grey ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Apolipoprotein E ◽  
Functional Decline ◽  
Prospective Analysis ◽  
Ε4 Allele

Apolipoprotein E Polymorphism in Elderly Chilean People with Alzheimer’s Disease

1998 ◽  
Vol 18 (1) ◽  
pp. 48-52 ◽  
Author(s):  
Pilar Quiroga ◽  
Carlos Calvo ◽  
Cecilia Albala ◽  
Julio Urquidi ◽  
JoséL. Santos ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Apolipoprotein E ◽  
Apolipoprotein E Polymorphism
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