Knockout of apolipoprotein A‐I decreases parenchymal and vascular β‐amyloid pathology in the Tg2576 mouse model of Alzheimer's disease

Contu, Laura; Carare, Roxana O.; Hawkes, Cheryl A.

doi:10.1111/nan.12556

Cited by 10 publications

(12 citation statements)

References 77 publications

(103 reference statements)

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“…Animal studies have illustrated that a lack of APOA-I exacerbates-while overexpression of human APOA-I alleviates-CAA in the APP/PS1 mouse model of AD, without affecting parenchymal Aβ deposition [83,84], consistent with a prior study in a different line of APOA-I-deficient AD mice (PD-APP) [85]. On the contrary, a recent study using another transgenic mouse model of AD (Tg2576) showed that lack of APOA-I decreased both parenchymal and vascular Aβ pathology [86]. However, another recent study with APP/PS1 mice extended prior findings, in which APOA-I deficiency increased CAA and neuroinflammation as well as cortical Aβ deposition [87].…”

Section: Amyloid Pathologysupporting

confidence: 87%

The Role of HDL and HDL Mimetic Peptides as Potential Therapeutics for Alzheimer’s Disease

Chernick

Zhong

2020

Biomolecules

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The role of high-density lipoproteins (HDL) in the cardiovascular system has been extensively studied and the cardioprotective effects of HDL are well established. As HDL particles are formed both in the systemic circulation and in the central nervous system, the role of HDL and its associated apolipoproteins in the brain has attracted much research interest in recent years. Alzheimer’s disease (AD) is the most prevalent neurodegenerative disorder and the leading cause of dementia worldwide, for which there currently exists no approved disease modifying treatment. Multiple lines of evidence, including a number of large-scale human clinical studies, have shown a robust connection between HDL levels and AD. Low levels of HDL are associated with increased risk and severity of AD, whereas high levels of HDL are correlated with superior cognitive function. Although the mechanisms underlying the protective effects of HDL in the brain are not fully understood, many of the functions of HDL, including reverse lipid/cholesterol transport, anti-inflammation/immune modulation, anti-oxidation, microvessel endothelial protection, and proteopathy modification, are thought to be critical for its beneficial effects. This review describes the current evidence for the role of HDL in AD and the potential of using small peptides mimicking HDL or its associated apolipoproteins (HDL-mimetic peptides) as therapeutics to treat AD.

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Section: Amyloid Pathologysupporting

confidence: 87%

The Role of HDL and HDL Mimetic Peptides as Potential Therapeutics for Alzheimer’s Disease

Chernick

Zhong

2020

Biomolecules

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“…Furthermore, apoa1 knockout mice show increased beta-amyloid (Aβ) deposition within the cerebrovascular wall and increased vascular inflammation. However, other studies reported either no difference [ 174 ] or reduced Aβ deposition within the vascular wall [ 175 ]. Mice overexpressing human APOA1 have reduced vascular inflammation and Aβ deposition [ 176 ].…”

Section: Hdl and Blood–brain Barrier Function In Stroke And Neurodegenerative Diseasesmentioning

confidence: 99%

The Endothelium Is Both a Target and a Barrier of HDL’s Protective Functions

Robert

Osto

Eckardstein

2021

Cells

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The vascular endothelium serves as a barrier between the intravascular and extravascular compartments. High-density lipoproteins (HDL) have two kinds of interactions with this barrier. First, bloodborne HDL must pass the endothelium to access extravascular tissues, for example the arterial wall or the brain, to mediate cholesterol efflux from macrophages and other cells or exert other functions. To complete reverse cholesterol transport, HDL must even pass the endothelium a second time to re-enter circulation via the lymphatics. Transendothelial HDL transport is a regulated process involving scavenger receptor SR-BI, endothelial lipase, and ATP binding cassette transporters A1 and G1. Second, HDL helps to maintain the integrity of the endothelial barrier by (i) promoting junction closure as well as (ii) repair by stimulating the proliferation and migration of endothelial cells and their progenitor cells, and by preventing (iii) loss of glycocalix, (iv) apoptosis, as well as (v) transmigration of inflammatory cells. Additional vasoprotective functions of HDL include (vi) the induction of nitric oxide (NO) production and (vii) the inhibition of reactive oxygen species (ROS) production. These vasoprotective functions are exerted by the interactions of HDL particles with SR-BI as well as specific agonists carried by HDL, notably sphingosine-1-phophate (S1P), with their specific cellular counterparts, e.g., S1P receptors. Various diseases modify the protein and lipid composition and thereby the endothelial functionality of HDL. Thorough understanding of the structure–function relationships underlying the multiple interactions of HDL with endothelial cells is expected to elucidate new targets and strategies for the treatment or prevention of various diseases.

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“…Spinster homolog 2 (SPNS2) regulates the levels of Sphingosine-1-phosphate (S1P) gradient that controls lymphocyte trafficking 23 . In addition, dnaJ homolog subfamily C member 25 (DNAJC25) can significantly increase cell apoptosis, and its overexpression inhibits cell growth 24 . Deletion of inositol polyphosphate multikinase (IPMK) in cell lines and mice virtually abolished lipophagy, caused liver damage and inflammation, and impaired hepatocyte regeneration 25 .…”

Section: Resultsmentioning

confidence: 99%

Genome Wide Analysis for Growth at Two Growth Stages in A New Fast-Growing Common Carp Strain (Cyprinus carpio L.)

Bouzoualegh

et al. 2020

Sci Rep

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tang 1,2 ✉ in order to identify candidate genes or loci associated with growth performance of the newly established common carp strain, Xinlong, we conducted a genome-wide association analysis using 2b-RAD technology on 123 individuals. We constructed two sets of libraries associated with growth-related parameters (weight, length, width and depth) measured at two different grow-out stages. Among the 413,059 SNPs identified using SOAP SNP calling, 147,131 were tested for GWAS after quality filtering. Finally, 39 overlapping SNPs, assigned to four genomic locations, were associated with growth traits in two stages. These loci were assigned to functional classes related to immune response, response to stress, neurogenesis, cholesterol metabolism and development, and proliferation and differentiation of cells. By overlapping results of Plink and EMMAX analyses, we identified three genes: TOX, PLK2 and CD163 (both methods P < 0.05). Our study results could be used for marker-assisted selection to further improve the growth of the Xinlong strain, and illustrate that largely different sets of genes drive the growth of carp in the early and late grow-out stages. Genome-wide association studies facilitate identification of single-nucleotide polymorphisms (SNPs) and genes associated with important economic traits. In particular, growth is one of the most economically important traits for the aquaculture industry. At the genomic level, genes and loci controlling this quantitative trait received a lot of interest in fish; for example growth rate in Atlantic salmon and rainbow trout 1-3 , head size in catfish and common carp 4,5 , etc. As a powerful statistical tool for connecting traits to their corresponding genes, genome-wide association study (GWAS) offers the possibility to analyze a massive amount of data. This allows identification of single nucleotide polymorphisms (SNP) or genes that may be related to important economic traits, or other traits of interest 6. However, GWAS employs methods that require genome-wide SNP data produced by genome re-sequencing, so it is relatively costly, which limits its applicability 7. Although the genechip used to capture the genome wide molecular markers has been established for some farmed animals (e.g. cattle and pigs), the application of GWAS in aquatic animals still faces higher costs and practical problems. To account for this, a simplified and cheaper genotyping method, 2b-RAD, was developed 8. This method is based on the sequencing of uniform DNA fragments produced by type IIB restriction endonuclease. Its effectiveness in associated analysis and genotyping has been established in several freshwater and marine fish species, including bighead carp (Hypophthalmichthys nobilis), Nile tilapia (Oreochromis niloticus), and yellowfin tuna (Thunnus albacares) 9-12. The common carp (Cyprinus carpio L.) is one of the oldest and most important farmed fish species, and the most widely distributed freshwater fish in the world 13,14. Ranking third among the most commercially important fish sp...

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Knockout of apolipoprotein A‐I decreases parenchymal and vascular β‐amyloid pathology in the Tg2576 mouse model of Alzheimer's disease

Cited by 10 publications

References 77 publications

The Role of HDL and HDL Mimetic Peptides as Potential Therapeutics for Alzheimer’s Disease

The Role of HDL and HDL Mimetic Peptides as Potential Therapeutics for Alzheimer’s Disease

The Endothelium Is Both a Target and a Barrier of HDL’s Protective Functions

Genome Wide Analysis for Growth at Two Growth Stages in A New Fast-Growing Common Carp Strain (Cyprinus carpio L.)

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