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Changes in climate trends and extreme climatic events are increasingly impacting on forests around the world. In order to better understand how and where major ecological and climatic changes will affect our forested ecosystems, tools based on landscape sensitivity analysis need to be developed to help inform sustainable forest management. This study was undertaken in the Northern Jarrah Forest (NJF) region in the Mediterranean climate of southwest Western Australia. Extreme drought and multiple heatwaves in 2010/2011 resulted in large-scale tree canopy dieback in the NJF. In this study, we used Landsat satellite imagery to (1) accurately map the damaged areas, (2) produce a damage probability model and (3) compare the model with a probability model derived from data collected through an airborne flight survey. We found that the Landsat-derived Normalized Difference Vegetation Indexwas a good indicator of drought/heat induced damagein the NJFregion. Both probability models identified the same set of topography and climate-related factors for determining the probability of drought/heat damage within the landscape. Extrapolation of the Landsat satellite method-based model, however, produced a more deterministic and useful drought/heat damage sensitivity map for the NJF region. The techniques and tools developed, and applied, in this study can readily be transferred to other regions around the world and can assist in the sustainable management and timely climate adaptation efforts to accommodate our future forests. [ABSTRACT FROM AUTHOR]

Two multicentre genome-wide association (GWA) studies provided substantial evidence, implicating the complement receptor 1 gene (CR1) in Alzheimer disease (AD) genetic etiology. CR1 encodes a large transmembrane receptor with a crucial role in the immune complement cascade. We performed a genetic follow-up of the GWA CR1 association in a Flanders-Belgian cohort (n=1883), and investigated the effect of single-nucleotide polymorphisms (SNPs) located in the CR1 locus on AD risk and cerebrospinal fluid (CSF) biomarker levels. We obtained significant association (Padj<0.03; odds ratio (OR)=1.24 (95% confidence interval (CI): 1.02-1.51)) for one CR1 risk haplotype, and haplotype association was strongest in individuals carrying apolipoprotein E (APOE) ɛ4 alleles (Padj<0.006; OR=1.50 (95% CI: 1.08-2.09)). Also, four SNPs correlated with increased CSF amyloid Aβ1−42 levels, suggesting a role for the CR1 protein in Aβ metabolism. Moreover, we quantified a low-copy repeat (LCR)-associated copy number variation (CNV) in CR1, producing different CR1 isoforms, CR1-F and CR1-S, and obtained significant association in carriers of CR1-S. We replicated the CR1 CNV association finding in a French cohort (n=2003) and calculated in the combined cohorts, an OR of 1.32; 95% CI: 1.10-1.59 (P=0.0025). Our data showed that the common AD risk association may well be explained by the presence of CR1-S increasing the number of C3b/C4b and cofactor activity sites and AD risk with 30% in CR1-S carriers. How precisely the different functional role of CR1-S in the immune complement cascade contributes to AD pathogenesis will need additional functional studies. [ABSTRACT FROM AUTHOR]

Apolipoprotein E (APOE) dependent lifetime risks (LTRs) for Alzheimer Disease (AD) are currently not accurately known and odds ratios alone are insufficient to assess these risks. We calculated AD LTR in 7351 cases and 10 132 controls from Caucasian ancestry using Rochester (USA) incidence data. At the age of 85 the LTR of AD without reference to APOE genotype was 11% in males and 14% in females. At the same age, this risk ranged from 51% for APOE44 male carriers to 60% for APOE44 female carriers, and from 23% for APOE34 male carriers to 30% for APOE34 female carriers, consistent with semi-dominant inheritance of a moderately penetrant gene. Using PAQUID (France) incidence data, estimates were globally similar except that at age 85 the LTRs reached 68 and 35% for APOE 44 and APOE 34 female carriers, respectively. These risks are more similar to those of major genes in Mendelian diseases, such as BRCA1 in breast cancer, than those of low-risk common alleles identified by recent GWAS in complex diseases. In addition, stratification of our data by age groups clearly demonstrates that APOE4 is a risk factor not only for late-onset but for early-onset AD as well. Together, these results urge a reappraisal of the impact of APOE in Alzheimer disease. [ABSTRACT FROM AUTHOR]

Since the first report showing that Alzheimer disease (AD) might be caused by mutations in the amyloid precursor protein gene ( APP), 20 different missense mutations have been reported. The majority of early-onset AD mutations alter processing of APP increasing relative levels of Aβ42 peptide, either by increasing Aβ42 or decreasing Aβ40 peptide levels or both. In a diagnostic setting using direct sequence analysis, we identified in one patient with familial early-onset AD a novel mutation in APP (c.2172G>C), predicting a K724N substitution in the intracytosolic fragment. The mutation is located downstream of the ε-cleavage site of APP and is the furthermost C-terminal mutation reported to date. In vitro expression of APP K724N cDNA showed an increase in Aβ42 and a decrease in Aβ40 levels resulting in a near three-fold increase of the Aβ42/Aβ40 ratio. Further, in vivo amyloid positron emission tomography (PET) imaging revealed significantly increased cortical amyloid deposits, supporting that in human this novel APP mutation is likely causing disease. Hum Mutat 27(9), 888-896, 2006. © 2006 Wiley-Liss, Inc. [ABSTRACT FROM AUTHOR]