Cardiovascular disease contributes to Alzheimer's disease: evidence from large-scale genome-wide association studies

Liu, Guiyou; Yao, Lifen; Liu, Jiafeng; Jiang, Yongshuai; Ma, Guoda; Chen, Zugen; Zhao, Bin; Li, Keshen

doi:10.1016/j.neurobiolaging.2013.10.084

Cited by 96 publications

(84 citation statements)

References 36 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Herein, using cardiac myocyte isolated from rat, we demonstrated that Erk1/2 and p38 MAPK is immediately and differentially regulated by Aβ [25][26][27][28][29][30][31][32][33][34][35] . Importantly, inhibition of the p38 pathway by its selective inhibitor SB203580 prevented Aβ-induced cardiac myocyte apoptosis, suggesting that activation of p38 through ER stress may plays a pivotal role in triggering Aβ-induced cellular dysfunction and potentially leads to the subsequent pathogenesis of cardiac amyloidosis.…”

Section: Introductionmentioning

confidence: 91%

“…The Aβ [25][26][27][28][29][30][31][32][33][34][35] fragment of the Alzheimer amyloid β-peptide, like its full-length peptide Aβ , has shown toxic activities in cultured cells [8,14]. The effect of Aβ (1-42) on cultured neurons is concentration-dependent, and significant cell loss was detected after treatment at concentrations of 20 μM.…”

Section: Effect Of Aβ 25-35 On the Viability Of Rat Cardiac Myocyte Imentioning

confidence: 99%

“…Although these Aβ concentrations are higher those seen in pathological conditions, low plasma Aβ levels could still cause a big negative impact due to extended stimulation [14][15][16][17]. We studied whether the fragment Aβ [25][26][27][28][29][30][31][32][33][34][35] has the ability to inhibit the growth of rat cardiac myocytes. The cell growth-inhibitory activity was determined by colorimetric measurement of cell viability.…”

Section: Effect Of Aβ 25-35 On the Viability Of Rat Cardiac Myocyte Imentioning

confidence: 99%

“…In order to detect Aβ [25][26][27][28][29][30][31][32][33][34][35] -mediated apoptosis in myocytes, the Hoechst and Annexin V/PI staining methods were applied. In Hoechst staining, control cells emitted a blue fluorescence with consistent nucleus intensity and presented a typical homogeneous distribution of chromatin in the nucleus.…”

Section: Aβ 25-35 Induced Cardiac Myocytes Apoptosisfigurementioning

confidence: 99%

See 3 more Smart Citations

The Toxicity Mechanisms of Action of Aβ25–35 in Isolated Rat Cardiac Myocytes

Zhang

Bian

et al. 2014

Molecules

View full text Add to dashboard Cite

β-Amyloid (Aβ) is deposited in neurons and vascular cells of the brain and is characterized as a pathologic feature of Alzheimer's disease (AD). Recently studies have reported that there is an association between cardiovascular risk factors and AD, however the mechanism of this association is still uncertain. In this study we observed Aβ had an effect on cardiovascular cells. We represent as a major discovery that Aβ 25-35 had toxicity on isolated rat cardiac myocytes by impacting the cytoskeleton assembly and causing ER stress, ultimately contributing to the apoptosis of the myocytes. Importantly, the activation of ER stress and subsequent cellular dysfunction and apoptosis by Aβ 25-35 was regulated by the MAPK pathway, which could be prevented by inhibition of p38 via pharmacological inhibitors. It was noteworthy that Aβ 25-35 played a critical role in cardiac myocytes, suggesting that Alzheimer's disease (AD) had a relation with the heart and understanding of these associations in future will help search for effective treatment strategies.

show abstract

Section: Introductionmentioning

confidence: 91%

Section: Effect Of Aβ 25-35 On the Viability Of Rat Cardiac Myocyte Imentioning

confidence: 99%

Section: Effect Of Aβ 25-35 On the Viability Of Rat Cardiac Myocyte Imentioning

confidence: 99%

Section: Aβ 25-35 Induced Cardiac Myocytes Apoptosisfigurementioning

confidence: 99%

See 2 more Smart Citations

The Toxicity Mechanisms of Action of Aβ25–35 in Isolated Rat Cardiac Myocytes

Zhang

Bian

et al. 2014

Molecules

View full text Add to dashboard Cite

show abstract

“…The P-values of MDMR became less significant as the gene size increased, while the aSPUset was robust to the number of SNPs. This locus containing APOE is well known to be related to Alzheimer's disease and cognitive impairment disorder (Seshadri et al 2010;Kamboh et al 2012;Liu et al 2014). Table 2 lists the SNPs included in the significant genes.…”

Section: Real Data Examplementioning

confidence: 99%

Powerful and Adaptive Testing for Multi-trait and Multi-SNP Associations with GWAS and Sequencing Data

Kim¹,

Zhang²,

Pan

2016

Genetics

View full text Add to dashboard Cite

Testing for genetic association with multiple traits has become increasingly important, not only because of its potential to boost statistical power, but also for its direct relevance to applications. For example, there is accumulating evidence showing that some complex neurodegenerative and psychiatric diseases like Alzheimer's disease are due to disrupted brain networks, for which it would be natural to identify genetic variants associated with a disrupted brain network, represented as a set of multiple traits, one for each of multiple brain regions of interest. In spite of its promise, testing for multivariate trait associations is challenging: if not appropriately used, its power can be much lower than testing on each univariate trait separately (with a proper control for multiple testing). Furthermore, differing from most existing methods for single-SNP-multiple-trait associations, we consider SNP set-based association testing to decipher complicated joint effects of multiple SNPs on multiple traits. Because the power of a test critically depends on several unknown factors such as the proportions of associated SNPs and of traits, we propose a highly adaptive test at both the SNP and trait levels, giving higher weights to those likely associated SNPs and traits, to yield high power across a wide spectrum of situations. We illuminate relationships among the proposed and some existing tests, showing that the proposed test covers several existing tests as special cases. We compare the performance of the new test with that of several existing tests, using both simulated and real data. The methods were applied to structural magnetic resonance imaging data drawn from the Alzheimer's Disease Neuroimaging Initiative to identify genes associated with gray matter atrophy in the human brain default mode network (DMN). For genomewide association studies (GWAS), genes AMOTL1 on chromosome 11 and APOE on chromosome 19 were discovered by the new test to be significantly associated with the DMN. Notably, gene AMOTL1 was not detected by single SNP-based analyses. To our knowledge, AMOTL1 has not been highlighted in other Alzheimer's disease studies before, although it was indicated to be related to cognitive impairment. The proposed method is also applicable to rare variants in sequencing data and can be extended to pathway analysis.KEYWORDS adaptive association test; ADNI; default mode network; gene-based test; imaging genetics; multiple traits A LZHEIMER'S disease (AD) (MIM 104300) is the most common neurodegenerative disease, and every 67 sec, someone in the United States develops AD (Alzheimer's Association 2015a). Currently there is no cure for AD, and most cases are diagnosed in the late stage of the disease. It is projected that the number of Americans of age 65 years and older with AD will increase from 5.1 million in 2015 to 13.5 million in 2050, a growth from an estimated 11% of the U.S. senior population in 2015 to 16% in 2050, costing .$1.1 trillion in 2050 (Alzheimer's Association 2015b). To advance our...

show abstract

Disease‐Specific Stem Cell Models for Toxicological Screenings and Drug Development

Jung

Schiller

et al. 2016

Stem Cells in Toxicology and Medicine

View full text Add to dashboard Cite

Cardiovascular disease contributes to Alzheimer's disease: evidence from large-scale genome-wide association studies

Cited by 96 publications

References 36 publications

The Toxicity Mechanisms of Action of Aβ25–35 in Isolated Rat Cardiac Myocytes

The Toxicity Mechanisms of Action of Aβ25–35 in Isolated Rat Cardiac Myocytes

Powerful and Adaptive Testing for Multi-trait and Multi-SNP Associations with GWAS and Sequencing Data

Disease‐Specific Stem Cell Models for Toxicological Screenings and Drug Development

Contact Info

Product

Resources

About