<i>APOE</i>Polymorphism Is Associated with C-reactive Protein Levels but Not with White Blood Cell Count: Dong-gu Study and Namwon Study

Yun, Yong Woon; Kweon, Sun-Seog; Choi, Jin Su; Rhee, Jung Ae; Lee, Young‐Hoon; Nam, Hae Sung; Jeong, Seul-Ki; Park, Kyeong Soo; Ryu, So Yeon; Choi, Seong Woo; Kim, Heung Dong; Cauley, Jane A.; Shin, Min Ho

doi:10.3346/jkms.2015.30.7.860

Cited by 11 publications

(11 citation statements)

References 40 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Greater Metabolic_risk (derived from body mass index, serum insulin and plasma triglyceride levels) was associated with higher serum CRP levels (β = 0.20 ± 0.076, p = 0.009). However, greater AD risk conferred by APOE genotype was associated with lower peripheral CRP (β = −0.17 ± 0.064, p = 0.019), consistent with previous reports (Yun et al, 2015). Metabolic risk did not have a significant direct effect on Brain_structure .…”

Section: Resultssupporting

confidence: 91%

See 1 more Smart Citation

Systemic inflammation as a predictor of brain aging: Contributions of physical activity, metabolic risk, and genetic risk

et al. 2018

View full text Add to dashboard Cite

Inflammatory processes may contribute to risk for Alzheimer's disease (AD) and age-related brain degeneration. Metabolic and genetic risk factors, and physical activity may, in turn, influence these inflammatory processes. Some of these risk factors are modifiable, and interact with each other. Understanding how these processes together relate to brain aging will help to inform future interventions to treat or prevent cognitive decline. We used brain magnetic resonance imaging (MRI) to scan 335 older adult humans (mean age 77.3 ± 3.4 years) who remained non-demented for the duration of the 9-year longitudinal study. We used structural equation modeling (SEM) in a subset of 226 adults to evaluate whether measures of baseline peripheral inflammation (serum C-reactive protein levels; CRP), mediated the baseline contributions of genetic and metabolic risk, and physical activity, to regional cortical thickness in AD-relevant brain regions at study year 9. We found that both baseline metabolic risk and AD risk variant apolipoprotein E ε4 (APOE4), modulated baseline serum CRP. Higher baseline CRP levels, in turn, predicted thinner regional cortex at year 9, and mediated an effect between higher metabolic risk and thinner cortex in those regions. A higher polygenic risk score composed of variants in immune-associated AD risk genes (other than APOE) was associated with thinner regional cortex. However, CRP levels did not mediate this effect, suggesting that other mechanisms may be responsible for the elevated AD risk. We found interactions between genetic and environmental factors and structural brain health. Our findings support the role of metabolic risk and peripheral inflammation in age-related brain decline.

show abstract

Section: Resultssupporting

confidence: 91%

“…APOE 4 has been associated previously with thinner cortex in older adults (Fan et al, 2010; Liu et al, 2010). A lower blood CRP level in APOE 4 carriers is also consistent with previous studies in humans (Hubacek et al, 2010; Yun et al, 2015). However, it is currently unclear what is mechanistically driving this relationship.…”

Section: Discussionsupporting

confidence: 92%

Systemic inflammation as a predictor of brain aging: Contributions of physical activity, metabolic risk, and genetic risk

et al. 2018

View full text Add to dashboard Cite

show abstract

“…Additionally, Bailey and colleagues [68] found that APOE ɛ4 carriers had smaller medial temporal lobe volumes and that the volume mediated the relationship between memory performance and APOE genotype. APOE ɛ4 is also associated with altered levels of C-reactive protein, a systemic marker of inflammation [69] which has been found to be associated with frailty, [70] memory performance and lower medial temporal volume [71], and cognitive decline in a non-demented population [72]. Taken together, frailty biomarkers, APOE , and age-related memory decline may share common pathophysiological mechanisms (i.e., brain atrophy, beta-amyloid burden, inflammatory markers) [73].…”

Section: Discussionmentioning

confidence: 99%

Frailty effects on non-demented cognitive trajectories are moderated by sex and Alzheimer’s genetic risk

et al. 2019

View full text Add to dashboard Cite

Background: Age-related frailty reflects cumulative multisystem physiological and health decline. Frailty increases the risk of adverse brain and cognitive outcomes, including differential decline and dementia. In a longitudinal sample of non-demented older adults, we examine whether (a) the level and/or change in frailty predicts trajectories across three cognitive domains (memory, speed, and executive function (EF)) and (b) prediction patterns are modified by sex or Alzheimer's genetic risk (Apolipoprotein E (APOE)). Methods: Participants (n = 632; M age = 70.7, range 53-95; 3 waves) were from the Victoria Longitudinal Study. After computing a frailty index, we used latent growth modeling and path analysis to test the frailty effects on level and change in three latent variables of cognition. We tested two potential moderators by stratifying by sex and APOE risk (ε4+, ε4-). Results: First, frailty levels predicted speed and EF performance (level) and differential memory change slopes. Second, change in frailty predicted the rate of decline for both speed and EF. Third, sex moderation analyses showed that females were selectively sensitive to (a) frailty effects on memory change and (b) frailty change effects on speed change. In contrast, the frailty effects on EF change were stronger in males. Fourth, genetic moderation analyses showed that APOE risk (e4+) carriers were selectively sensitive to frailty effects on memory change. Conclusion: In non-demented older adults, increasing frailty is strongly associated with the differential decline in cognitive trajectories. For example, higher (worse) frailty was associated with more rapid memory decline than was lower (better) frailty. These effects, however, are moderated by both genetic risk and sex.

show abstract

“…Surprisingly, however, this is not the case, at least with CRP. Studies have consistently shown that CRP levels are lower in APOEε4 carriers ( Ukkola et al, 2009 ; Lima et al, 2014 ; Metti et al, 2014 ; Yun et al, 2015 ). Marz et al (2004) proposed that the metabolism of CRP might be associated with the mevalonate/cholesterol synthetic pathway, which might be downregulated in APOEε4 carriers.…”

Section: Apoeε4 Inflammation and Alzheimer’s Diseasementioning

confidence: 99%

Inflammation: Bridging Age, Menopause and APOEε4 Genotype to Alzheimer’s Disease

Mishra

Brinton

2018

Front. Aging Neurosci.

View full text Add to dashboard Cite

Neuro-inflammatory processes that contribute to development of Alzheimer’s are evident early in the latent prodromal phase and worsen during the course of the disease. Despite substantial mechanistic and clinical evidence of inflammation, therapeutic approaches targeting inflammation have failed to alter the course of the disease. Disparate results from epidemiological and clinical trials targeting inflammation, highlight the complexity of the inflammatory process. Herein we review the dynamics of the inflammatory process across aging, midlife endocrine transitions, and the APOEε4 genotype and their contribution to progression of Alzheimer’s disease (AD). We discuss the chronic inflammatory processes that are activated during midlife chronological and endocrine aging, which ultimately limit the clearance capacity of microglia and lead to immune senescence. Aging, menopause, and APOEε4 combine the three hits of a compromised bioenergetic system of menopause with the chronic low grade innate inflammation of aging with the APOEε4 dyslipidemia and adaptive immune response. The inflammatory immune response is the unifying factor that bridges across each of the risk factors for AD. Immune system regulators that are specific to stage of disease and inflammatory phenotype would provide a therapeutic strategy to disconnect the bridge that drives disease. Outcomes of this analysis provide plausible mechanisms underlying failed clinical trials of anti-inflammatory agents in Alzheimer’s patients. Further, they highlight the need for stratifying AD clinical trial cohorts based on inflammatory phenotype. Combination therapies that include targeted use of anti-inflammatory agent’s specific to the immune phenotype are considered.

show abstract

APOEPolymorphism Is Associated with C-reactive Protein Levels but Not with White Blood Cell Count: Dong-gu Study and Namwon Study

Cited by 11 publications

References 40 publications

Systemic inflammation as a predictor of brain aging: Contributions of physical activity, metabolic risk, and genetic risk

Systemic inflammation as a predictor of brain aging: Contributions of physical activity, metabolic risk, and genetic risk

Frailty effects on non-demented cognitive trajectories are moderated by sex and Alzheimer’s genetic risk

Inflammation: Bridging Age, Menopause and APOEε4 Genotype to Alzheimer’s Disease

Contact Info

Product

Resources

About