Table_2_Associations of apolipoprotein E ε4 allele, regional cerebral blood flow, and serum liver function markers in patients with cognitive impairment.xlsx

IntroductionThe ε4 allele of the apolipoprotein E gene (APOE4) is expressed abundantly in both the brain and peripheral circulation as a genetic risk factor for Alzheimer’s disease (AD). Cerebral blood flow (CBF) dysfunction is an essential feature of AD, and the liver plays an important role in the pathogenesis of dementia. However, the associations of APOE4 with CBF and liver function markers in patients with cognitive impairment remains unclear. We aimed to evaluate the associations of APOE4 with CBF measured by arterial spin labeling (ASL) magnetic resonance imaging (MRI) and serum liver function markers in participants who were diagnosed with cognitive impairment.MethodsFourteen participants with AD and sixteen with amnestic mild cognitive impairment (MCI) were recruited. In addition to providing comprehensive clinical information, all patients underwent laboratory tests and MRI. All participants were divided into carriers and noncarriers of the ε4 allele, and T-tests and Mann–Whitney U tests were used to observe the differences between APOE4 carriers and noncarriers in CBF and liver function markers.ResultsRegarding regional cerebral blood flow (rCBF), APOE4 carriers showed hyperperfusion in the bilateral occipital cortex, bilateral thalamus, and left precuneus and hypoperfusion in the right lateral temporal cortex when compared with noncarriers. Regarding serum liver function markers, bilirubin levels (including total, direct, and indirect) were lower in APOE4 carriers than in noncarriers.ConclusionAPOE4 exerts a strong effect on CBF dysfunction by inheritance, representing a risk factor for AD. APOE4 may be related to bilirubin metabolism, potentially providing specific neural targets for the diagnosis and treatment of AD.</p

Table_3_Associations of apolipoprotein E ε4 allele, regional cerebral blood flow, and serum liver function markers in patients with cognitive impairment.xlsx

IntroductionThe ε4 allele of the apolipoprotein E gene (APOE4) is expressed abundantly in both the brain and peripheral circulation as a genetic risk factor for Alzheimer’s disease (AD). Cerebral blood flow (CBF) dysfunction is an essential feature of AD, and the liver plays an important role in the pathogenesis of dementia. However, the associations of APOE4 with CBF and liver function markers in patients with cognitive impairment remains unclear. We aimed to evaluate the associations of APOE4 with CBF measured by arterial spin labeling (ASL) magnetic resonance imaging (MRI) and serum liver function markers in participants who were diagnosed with cognitive impairment.MethodsFourteen participants with AD and sixteen with amnestic mild cognitive impairment (MCI) were recruited. In addition to providing comprehensive clinical information, all patients underwent laboratory tests and MRI. All participants were divided into carriers and noncarriers of the ε4 allele, and T-tests and Mann–Whitney U tests were used to observe the differences between APOE4 carriers and noncarriers in CBF and liver function markers.ResultsRegarding regional cerebral blood flow (rCBF), APOE4 carriers showed hyperperfusion in the bilateral occipital cortex, bilateral thalamus, and left precuneus and hypoperfusion in the right lateral temporal cortex when compared with noncarriers. Regarding serum liver function markers, bilirubin levels (including total, direct, and indirect) were lower in APOE4 carriers than in noncarriers.ConclusionAPOE4 exerts a strong effect on CBF dysfunction by inheritance, representing a risk factor for AD. APOE4 may be related to bilirubin metabolism, potentially providing specific neural targets for the diagnosis and treatment of AD.</p

Table_1_Associations of apolipoprotein E ε4 allele, regional cerebral blood flow, and serum liver function markers in patients with cognitive impairment.xlsx

IntroductionThe ε4 allele of the apolipoprotein E gene (APOE4) is expressed abundantly in both the brain and peripheral circulation as a genetic risk factor for Alzheimer’s disease (AD). Cerebral blood flow (CBF) dysfunction is an essential feature of AD, and the liver plays an important role in the pathogenesis of dementia. However, the associations of APOE4 with CBF and liver function markers in patients with cognitive impairment remains unclear. We aimed to evaluate the associations of APOE4 with CBF measured by arterial spin labeling (ASL) magnetic resonance imaging (MRI) and serum liver function markers in participants who were diagnosed with cognitive impairment.MethodsFourteen participants with AD and sixteen with amnestic mild cognitive impairment (MCI) were recruited. In addition to providing comprehensive clinical information, all patients underwent laboratory tests and MRI. All participants were divided into carriers and noncarriers of the ε4 allele, and T-tests and Mann–Whitney U tests were used to observe the differences between APOE4 carriers and noncarriers in CBF and liver function markers.ResultsRegarding regional cerebral blood flow (rCBF), APOE4 carriers showed hyperperfusion in the bilateral occipital cortex, bilateral thalamus, and left precuneus and hypoperfusion in the right lateral temporal cortex when compared with noncarriers. Regarding serum liver function markers, bilirubin levels (including total, direct, and indirect) were lower in APOE4 carriers than in noncarriers.ConclusionAPOE4 exerts a strong effect on CBF dysfunction by inheritance, representing a risk factor for AD. APOE4 may be related to bilirubin metabolism, potentially providing specific neural targets for the diagnosis and treatment of AD.</p

Table_4_Associations of apolipoprotein E ε4 allele, regional cerebral blood flow, and serum liver function markers in patients with cognitive impairment.xlsx

IntroductionThe ε4 allele of the apolipoprotein E gene (APOE4) is expressed abundantly in both the brain and peripheral circulation as a genetic risk factor for Alzheimer’s disease (AD). Cerebral blood flow (CBF) dysfunction is an essential feature of AD, and the liver plays an important role in the pathogenesis of dementia. However, the associations of APOE4 with CBF and liver function markers in patients with cognitive impairment remains unclear. We aimed to evaluate the associations of APOE4 with CBF measured by arterial spin labeling (ASL) magnetic resonance imaging (MRI) and serum liver function markers in participants who were diagnosed with cognitive impairment.MethodsFourteen participants with AD and sixteen with amnestic mild cognitive impairment (MCI) were recruited. In addition to providing comprehensive clinical information, all patients underwent laboratory tests and MRI. All participants were divided into carriers and noncarriers of the ε4 allele, and T-tests and Mann–Whitney U tests were used to observe the differences between APOE4 carriers and noncarriers in CBF and liver function markers.ResultsRegarding regional cerebral blood flow (rCBF), APOE4 carriers showed hyperperfusion in the bilateral occipital cortex, bilateral thalamus, and left precuneus and hypoperfusion in the right lateral temporal cortex when compared with noncarriers. Regarding serum liver function markers, bilirubin levels (including total, direct, and indirect) were lower in APOE4 carriers than in noncarriers.ConclusionAPOE4 exerts a strong effect on CBF dysfunction by inheritance, representing a risk factor for AD. APOE4 may be related to bilirubin metabolism, potentially providing specific neural targets for the diagnosis and treatment of AD.</p

The allele frequencies of HLA-DRB1*0301 and HLA-DRB1*0406 in populations from various ethnic regions.

<p>These data information were collected from the Allele Frequency Net Database <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0048594#pone.0048594-GonzalezGalarza1" target="_blank">[52]</a> except reference 25,27–30,33–34,38–39,41,45,51. Allele Frequency: Total number of copies of the allele in the population sample (Alleles/2n) in decimal format. a: data from Chinese National Marrow Donor Program(CMDP), b: data from Tzu Chi Taiwan Marrow Donor Registry (TCTMDR), c: data from USA Colorado Univ. Cord Blood Bank, d: data from Poland DKMS, e: data from Umbilical Cord Blood Bank of Bacelona, f: data in Allele frequency net was calculated from Phenotype Frequencies assuming Hardy-Weinberg proportions.</p

Comparison of the allele frequencies of HLA-DRB1*0301 among various groups.

<p>All subjects were classified by gender and age of onset of Parkinson’s disease (PD). △Pc<0.05 the allele frequency of HLA-DRB1*0301 in PD patients(total) vs. the one in healthy control(total), *Pc<0.05 the allele frequency of HLA-DRB1*0301 in PD patients (onset age ≤50) vs. the one in healthy control subgroup (onset age ≤50), # Pc<0.05 the allele frequency of HLA-DRB1*0301 in PD patients (onset age ≤50) vs. the one in PD patients (onset age >50).</p

Forest plots summarizing the Allele frequency of HLA-DRB1*0301 in Asian and European ancestry populations from various regions.

<p>The allele frequency was indicated as ES (95%CI). The distribution of HLA-DRB1*0301 was inequality in the worldwide populations, European ancestry populations presented a higher allele frequency of HLA-DRB1*0301 than African and Latin American ancestry populations and Asians (0.114 Vs. 0.071, 0.069, 0.041). In intra-Asian, Taiwanese presented a higher allele frequency of HLA-DRB1*0301 than populations in USA, mainland China, and Korea(0.091 Vs.0.054, 0.047, 0.022). However, HLA-DRB1*0301 was a rare allele in Japanese.</p

Basic information of patients with sporadic Parkinson’s disease (PD) and healthy controls.

<p>Basic information of patients with sporadic Parkinson’s disease (PD) and healthy controls.</p

Frequencies of HLA-DRB1 phenotypes and alleles in patients with Parkinson’s disease (PD) and healthy controls.

<p>Phenotype Frequency (Allele Frequency) was presented in every cell. “−”: the allele was not been detected. Phenotype Frequency: Percentage of individuals who have the allele (Individuals/N) in percentage format. Allele Frequency: Total number of copies of the allele in the population sample (Alleles/2N) in decimal format, Pc = correction of P value (Bonferroni adjustment), Pc<0.05 is considered as significant, ns = not significant. Patients had significant higher frequencies of HLA-DRB1*0301 and lower frequency of HLA-DRB1*0406 than healthy controls did.</p

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<p>Alzheimer’s disease (AD) is a progressive neurodegenerative disorder that has proved refractory to drug treatment. Given evidence of neuroprotection in animal models of ischemic stroke, we assessed the prenylflavonoid xanthohumol from the Common Hop (Humulus lupulus L.) for therapeutic potential in murine neuroblastoma N2a cells stably expressing human Swedish mutant amyloid precursor protein (N2a/APP), a well-characterized cellular model of AD. The ELISA and Western-blot analysis revealed that xanthohumol (Xn) inhibited Aβ accumulation and APP processing, and that Xn ameliorated tau hyperphosphorylation via PP2A, GSK3β pathways in N2a/APP cells. The amelioration of tau hyperphosphorylation by Xn was also validated on HEK293/Tau cells, another cell line with tau hyperphosphorylation. Proteomic analysis (2D-DIGE-coupled MS) revealed a total of 30 differentially expressed lysate proteins in N2a/APP vs. wild-type (WT) N2a cells (N2a/WT), and a total of 21 differentially expressed proteins in lysates of N2a/APP cells in the presence or absence of Xn. Generally, these 51 differential proteins could be classified into seven main categories according to their functions, including: endoplasmic reticulum (ER) stress-associated proteins; oxidative stress-associated proteins; proteasome-associated proteins; ATPase and metabolism-associated proteins; cytoskeleton-associated proteins; molecular chaperones-associated proteins, and others. We used Western-blot analysis to validate Xn-associated changes of some key proteins in several biological/pathogenic processes. Taken together, we show that Xn reduces AD-related changes in stably transfected N2a/APP cells. The underlying mechanisms involve modulation of multiple pathogenic pathways, including those involved in ER stress, oxidative stress, proteasome molecular systems, and the neuronal cytoskeleton. These results suggest Xn may have potential for the treatment of AD and/or neuropathologically related neurodegenerative diseases.</p