Meta-Analysis of Peripheral Blood Apolipoprotein E Levels in Alzheimer’s Disease

Wang, Chong; Yu, Jin‐Tai; Wang, Hui-Fu; Jiang, Teng; Tan, Cheng; Meng, Xiangyi; Soares, Holly; Tan, Lan

doi:10.1371/journal.pone.0089041

Cited by 37 publications

(30 citation statements)

References 39 publications

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“…We found that there was no difference in the amount of plasma ApoE within the same APOE genotype carriers, irrespective of their clinical status. However, consistent with previous studies (Gupta et al, 2011;Wang et al, 2014), APOE2 carriers had the highest levels of plasma ApoE while APOE4 carriers have the lowest (Fig. 6A and B).…”

Section: Plasma Apoe Levels In Different Apoe Carrierssupporting

confidence: 92%

“…The peptides were dissolved in Tris-buffered saline (TBS, 20 mM Tris-HCl and 150 mM NaCl, pH = 7.4) and stored at −20°C until further use. The final concentration of ApoE in our experiment was 40 mg/L, which represents the physiological concentration of ApoE in human plasma (Wang et al, 2014). In addition, lipidated ApoE isoforms were obtained from our collaborators: Prof. Ralph Martins and Ian Martins (Edith Cowan University)…”

Section: Apoe Preparationmentioning

confidence: 99%

“…Total plasma ApoE levels have been reported to be significantly lower in AD patients, irrespective of APOE genotypes and APOE4 carriers exhibited the largest decrease in total plasma ApoE levels (Gupta et al, 2011;Wang et al, 2014). Likewise, several studies have also reported genotype-dependent variability in ApoE levels in the brain with the lowest concentrations found in APOE4 carriers (Hudry et al, 2013;Riddell et al, 2008;Ulrich et al, 2013).…”

Section: Introductionmentioning

confidence: 98%

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Zinc affects the proteolytic stability of Apolipoprotein E in an isoform-dependent way

Gupta

Martins

et al. 2015

Neurobiology of Disease

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The pathological role of zinc in Alzheimer's disease (AD) is not yet fully elucidated, but there is strong evidence that zinc homeostasis is impaired in the AD brain and that this contributes to disease pathogenesis. In this study we examined the effects of zinc on the proteolysis of synthetic Apolipoprotein E (ApoE), a protein whose allelic variants differentially contribute to the onset/progression of disease. We have demonstrated that zinc promotes the proteolysis (using plasma kallikrein, thrombin and chymotrypsin) of synthetic ApoE in an isoform-specific way (E4>E2 and E3), resulting in more ApoE fragments, particularly for ApoE4. In the absence of exogenous proteases there was no effect of metal modulation on either lipidated or non-lipidated ApoE isoforms. Thus, increased zinc in the complex milieu of the ageing and AD brain could reduce the level of normal full-length ApoE and increase other forms that are involved in neurodegeneration. We further examined human plasma samples from people with different ApoE genotypes. Consistent with previous studies, plasma ApoE levels varied according to different genotypes, with ApoE2 carriers showing the highest total ApoE levels and ApoE4 carriers the lowest. The levels of plasma ApoE were not affected by either the addition of exogenous metals (copper, zinc or iron) or by chelation. Taken together, our study reveals that zinc may contribute to the pathogenesis of AD by affecting the proteolysis of ApoE, which to some extent explains why APOE4 carriers are more susceptible to AD.

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Section: Plasma Apoe Levels In Different Apoe Carrierssupporting

confidence: 92%

Section: Apoe Preparationmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 98%

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Zinc affects the proteolytic stability of Apolipoprotein E in an isoform-dependent way

Gupta

Martins

et al. 2015

Neurobiology of Disease

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“…Polymorphisms at the ApoE promotor region have been observed to affect the levels of ApoE expression, which is also thought to be important in the development of AD. A metaanalysis revealed that lower levels of plasma ApoE are present in AD [109]. This is further confirmed in a study that used Mendelian randomization to eliminate confounding factors and using various alleles in the promotor region of ApoE, which causes lower levels of plasma ApoE minimizing reverse causation.…”

Section: Apoementioning

confidence: 77%

Targeting Alzheimer's disease with gene and cell therapies

et al. 2018

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Alzheimer's disease (AD) causes dementia in both young and old people affecting more than 40 million people worldwide. The two neuropathological hallmarks of the disease, amyloid beta (Aβ) plaques and neurofibrillary tangles consisting of protein tau are considered the major contributors to the disease. However, a more complete picture reveals significant neurodegeneration and decreased cell survival, neuroinflammation, changes in protein and energy homeostasis and alterations in lipid and cholesterol metabolism. In addition, gene and cell therapies for severe neurodegenerative disorders have recently improved technically in terms of safety and efficiency and have translated to the clinic showing encouraging results. Here, we review broadly current data within the field for potential targets that could modify AD through gene and cell therapy strategies. We envision that not only Aβ will be targeted in a disease-modifying treatment strategy but rather that a combination of treatments, possibly at different intervention times may prove beneficial in curing this devastating disease. These include decreased tau pathology, neuronal growth factors to support neurons and modulation of neuroinflammation for an appropriate immune response. Furthermore, cell based therapies may represent potential strategies in the future.

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“…Therefore, in the last years a great effort has been devoted to determine molecular markers for robust, and if possible, early diagnostics of AD. The protein analysis of cerebrospinal fluid (CSF) (βA 1-42 (INNOTEST®), ApoE, tau and phosphorylated tau is now considered the most precise method for the diagnostic of AD [12][13][14][15]. Attempts to develop less invasive methods were published based on the detection of multiple plasma molecular markers (between 18 and 89) that showed a precision of 70% for early detection of CI and AD [16,17].…”

Section: Investigation and Diagnostic Of Cognitive Impairment And Alzmentioning

confidence: 99%

Gut Microbiota, a Key Factor Relating Diet and Inflammation with the Progression of Cognitive Impairment in Older People

Pérez-Martı́nez¹

2017

JNHFE

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Developed societies are facing a remarkable increase of population's longevity and, consequently, of chronic diseases such as obesity, cardiovascular or neurodegenerative diseases. Age associated cognitive impairment (CI) (dementia) in its different forms represent a real social, economic and public health problem, and particularly the severe and highly prevalent Alzheimer disease (AD). Inflammation and altered metabolism of neurotransmitters and hormones are common in elderly suffering CI and AD. Metagenomics studies have demonstrated that in normal adult population, as well as in older people, health status and diet are the main factors affecting microbiota composition. Older persons frequently develop immune system degeneration leading to a low response to antigens and to a low profile persistent inflammation (inflammaging). Data from elderly populations and disease models show that systemic inflammation alters gut microbiota and also certain changes in the microbiota induce inflammatory secretions. In addition, there is a more than likely role of gut microbiota in the gut-brain signalling through the synthesis and processing of neurotransmitters. Hence, changes occurring in the gut microbiota of the elderly mostly due to diet, environment and inflammatory processes might be associated to brain function. The objective of this review would be to show that there are evidences that link gut microbiota and cognitive decline through inflammatory processes, although direct action on neurotransmitters may not be discarded. Research data shown here supports the view that inflammation linked to neurodegenerative diseases associated to ageing, may cause changes in the gut microbiota composition that, turn, would feed inflammation and aggravating the disease. This perverse cycle has been delayed to a certain extent through a healthy diet rich in complex carbohydrates, such as the Mediterranean diet.

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Meta-Analysis of Peripheral Blood Apolipoprotein E Levels in Alzheimer’s Disease

Cited by 37 publications

References 39 publications

Zinc affects the proteolytic stability of Apolipoprotein E in an isoform-dependent way

Zinc affects the proteolytic stability of Apolipoprotein E in an isoform-dependent way

Targeting Alzheimer's disease with gene and cell therapies

Gut Microbiota, a Key Factor Relating Diet and Inflammation with the Progression of Cognitive Impairment in Older People

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