Distribution of <i>PSEN1</i> p.E318G mutation carriers in CSF Biomarker quartiles.

<p><b>A</b>. CSF tau, Logistic regression model p = 6.0×10⁻⁴. <b>B</b>. CSF pTau, Logistic regression model p = 3.0×10⁻⁴. <b>C</b>. CSF Aβ42, Logistic regression model p = 0.38. White bars represent the number of non carriers. Black bars represent the number of carriers <b>D</b>. Association of <i>PSEN1</i> gene with CSF tau. <b>E</b>. Association of <i>PSEN1</i> gene with CSF ptau. <b>F</b>. Association of <i>PSEN1</i> gene with CSF Aβ42. Plots are showing the most significant SNP at a given locus along with the combined-analysis results for SNPs in the region surrounding it (typically ±500 kb). Symbols are colored according to the LD of the SNP with the top SNP (r² color-based insert). The red line represents the threshold for significance. The light blue line represents the estimated recombination rate. <b>G</b>. LD Block for the most significant SNP associated with biomarker levels at <i>PSEN1</i> genomic region: SNP rs76342307 based on the 1000 genome project for Europeans. Gene annotations are shown as dark green lines. <b>H</b>. LD Block for rs76342307 and rs17125721 in our own data set. <b>I</b>. Plot after the conditional analysis including both SNPs (rs76342307 and rs17125721) in the model.</p

Frequency of the rare variants in cases and controls and in individuals with and without Aβ deposition.

<p>Gene: official Symbol provide by HGNC; AA Substitution: amino acid change resulting from the observed variant; CDR at the time of the Lumbar punction. Samples were stratified based on the CSF Aβ42 levels as an approximation to the Aβ deposition. For ADNI-CSF series the cut-off was Aβ42 = 192 pg/mL and in WU-ADRC-CSF series we used a CSF Aβ42 = 500 pg/mL.</p

<i>PSEN1</i>, p.E318G modifies Alzheimer's risk in <i>APOE</i> e4 carriers.

<p><i>PSEN1</i>, p.E318G modifies Alzheimer's risk in <i>APOE</i> e4 carriers.</p

Summary of the rare variants found in the extreme values of CSF biomarker levels.

<p>Gene: official Symbol provide by HGNC; dbSNP: variants with or without rs numbers. AA Substitution: amino acid change resulting from the observed variant; dbSNP ID: rs# for variants present in dbSNP 135, Novel for variants not present in dbsnp, 1000 genome or Exome Variant Server; GERP score: Genomic Evolutionary Rate Profiling score; Protein prediction: based on SIFT/Polyphen2 analysis of the predicted effect of the substitution on protein function; MAF in ESV: Minor allele frequency in Exome Variant Server; Total # Hets: Number of carriers of the variant in the total sample; Total MAF: Minor allele frequency in all sample genotyped. Clinical Interpretation: Clinical interpretation is based on AD&FTD mutation database and published papers.</p>§<p>dbSNP 135 appears as validation pending</p

Effect of the interaction of <i>PSEN1</i> p.E318G with <i>APOE</i> in individuals with and without Aβ deposition.

<p>Samples were stratified based on the CSF Aβ42 levels as an approximation to the Aβ deposition. For ADNI-CSF series the cut-off was Aβ42 = 192 pg/mL and in WU-ADRC-CSF series we used a CSF Aβ42 = 500 pg/mL.</p

Distribution of biomarker levels in <i>PSEN1</i> p.E318G and <i>APOE</i> carriers.

<p>Distribution of the covariate-adjusted residuals of the CSF tau, ptau, Aβ42, Tau∶Aβ42 and ptau∶Aβ42 ratio. <b>A</b>. <i>APOE</i> ε4 positive/<i>PSEN1</i> p.E318G carriers and. <b>B</b>. <i>APOE</i> ε4 negative/<i>PSEN1</i> p.E318G carriers. <b>C</b>. Forest plot of the odd ratios of the effect of <i>PSEN1</i> p.E318G in <i>APOE</i> ε4 heterozygous. <b>D</b>. Pedigrees for some of the families with p.E318G carriers illustrating the segregation analysis and the presence of <i>APOE</i> ε4 allele. A/G or A/A is the genotype for p.E318G variant. 2/3, 3/3, 3/4, 4/4 is the APOE genotype. * Symbol means confirmed AD by autopsy. Δ Symbol indicates probable AD diagnosed using NINCDS-ADRDA criteria.</p

Summary of sample characteristics.

<p>Age at lumbar puncture (LP), percentage of females, percentage of <i>APOE4</i> allele carriers, clinical dementia rating (CDR) at LP date for each sample and percentage of individuals with Low (L) levels of Aβ42 normalized for each site (see <a href="http://www.plosgenetics.org/article/info:doi/10.1371/journal.pgen.1003685#s4" target="_blank">methods</a>). For each phenotype the median in pg/ml and the range is shown. Charles F. and Joanne Knight Alzheimer's Disease Research Center at University of Washington (WU-ADRC) and Alzheimer's Disease Neuroimaging Initiative (ADNI). Cerebrospinal Fluid (CSF).</p

Identifying a Sustained Pathway to Multidimensional Poverty Reduction: Evidence from Two Chinese Provinces

Poor rural households in developing countries often endure many-faceted burdens including monetary poverty, nutrition deficiency and energy shortage due to reliance on limited local natural resources with low utilisation efficiency. We investigate a sustained pathway in rural China to escape the vicious circle between three important dimensions of poverty – deficiency of income, malnutrition and low energy consumption profile in terms of reliance on firewood. By exploiting household panel data, we identify three inter-locking deprivations. Firewood plantations offer short-term solutions to break them through income effects, while the effective long-term means are increasing agricultural labour productivity and provision of agricultural loans. There are no household-level returns to rural electrification or infrastructure.This research is supported by the Fundamental Research Funds for the Central Universities, and the Research Funds of Renmin University of China (Grant No.: 15XNA005)