New insights from XRF core scanning data into boreal lake ontogeny during the Eemian (Marine Isotope Stage 5e) at Sokli, northeast Finland

Biological proxies from the Sokli Eemian (Marine Isotope Stage 5e) paleolake sequence from northeast Finland have previously shown that, unlike many postglacial records from boreal sites, the lake becomes increasingly eutrophic over time. Here, principal components (PC) were extracted from a high resolution multi-element XRF core scanning dataset to describe minerogenic input from the wider catchment (PC1), the input of S, Fe, Mn, and Ca-rich detrital material from the surrounding Sokli Carbonatite Massif (PC2), and chemical weathering (PC3). Minerogenic inputs to the lake were elevated early in the record and during two abrupt cooling events when soils and vegetation in the catchment were poor. Chemical weathering in the catchment generally increased over time, coinciding with higher air temperatures, catchment productivity, and the presence of acidic conifer species. Abiotic edaphic processes play a key role in lake ontogeny at this site stemming from the base cation- and nutrient-rich bedrock, which supports lake alkalinity and productivity. The climate history at this site, and its integrated effects on the lake system, appear to override development processes and alters its long-term trajectory.Peer reviewe

New insights into the genetic etiology of Alzheimer's disease and related dementias

Characterization of the genetic landscape of Alzheimer's disease (AD) and related dementias (ADD) provides a unique opportunity for a better understanding of the associated pathophysiological processes. We performed a two-stage genome-wide association study totaling 111,326 clinically diagnosed/'proxy' AD cases and 677,663 controls. We found 75 risk loci, of which 42 were new at the time of analysis. Pathway enrichment analyses confirmed the involvement of amyloid/tau pathways and highlighted microglia implication. Gene prioritization in the new loci identified 31 genes that were suggestive of new genetically associated processes, including the tumor necrosis factor alpha pathway through the linear ubiquitin chain assembly complex. We also built a new genetic risk score associated with the risk of future AD/dementia or progression from mild cognitive impairment to AD/dementia. The improvement in prediction led to a 1.6- to 1.9-fold increase in AD risk from the lowest to the highest decile, in addition to effects of age and the APOE ε4 allele

Multiancestry analysis of the HLA locus in Alzheimer’s and Parkinson’s diseases uncovers a shared adaptive immune response mediated by HLA-DRB1*04 subtypes

Across multiancestry groups, we analyzed Human Leukocyte Antigen (HLA) associations in over 176,000 individuals with Parkinson’s disease (PD) and Alzheimer’s disease (AD) versus controls. We demonstrate that the two diseases share the same protective association at the HLA locus. HLA-specific fine-mapping showed that hierarchical protective effects of HLA-DRB1*04 subtypes best accounted for the association, strongest with HLA-DRB1*04:04 and HLA-DRB1*04:07, and intermediary with HLA-DRB1*04:01 and HLA-DRB1*04:03. The same signal was associated with decreased neurofibrillary tangles in postmortem brains and was associated with reduced tau levels in cerebrospinal fluid and to a lower extent with increased Aβ42. Protective HLA-DRB1*04 subtypes strongly bound the aggregation-prone tau PHF6 sequence, however only when acetylated at a lysine (K311), a common posttranslational modification central to tau aggregation. An HLA-DRB1*04-mediated adaptive immune response decreases PD and AD risks, potentially by acting against tau, offering the possibility of therapeutic avenues

Can XRF scanning of speleothems be used as a non-destructive method to identify paleoflood events in caves?

We have developed a novel, quick and non-destructive method for tracing flood events in caves through the analysis of a stalagmite thick section with an XRF core scanner. The analyzed stalagmite has multiple horizons of fine sediments from past flood events intercalated with areas of cleaner calcite. Flood events detected from the elemental XRF core scanning data show good agreement with the position of flood horizons identified in petrographic thin sections. The geochemical composition of the individual flood layers shows that in certain cases the clay horizons had a distinct geochemical fingerprint suggesting that it may be possible to distinguish individual flood layers based on their geochemistry. This presents the possibility for using flood events as marker horizons to chronologically tie different speleothems in a cave to each other

The Itrax and organic rich sediments: Tephrochronologyand humification

Holocene records of climate change can be derived from organic rich sediments such as peats (with organic contents >99%) and gyttja rich lake sediments. While the performance of the Itrax is generally negatively affected by higher organic matter contents, we are currently developing two separate Itrax applications for such sediments. Tephras are an important part of establishing good chronologies for Holocene sequences. Tephras can vary in thickness from a few centimeters to a few shards thick. Finding crypotephra (i.e., those tephra not visible to the naked eye) is a time consuming process involving tedious sub-sampling and density separations. In order to improve the efficiency of tephra extraction we are developing a method to ‘screen’ sediment cores for tephra. Using small step sizes (<1 mm), we identify areas where changes in the sample matrix (signaled through changes in the mean standard error) and elemental chemistry suggest the possible presence of tephra. These ‘target depths’ are then sub-sampled at a higher resolution (1 cm vs. 5 cm) for tephra extraction. To date we have tested three different sites and shard counts made at target depths shows that the Itrax can successfully locate both rhyolitic and basaltic tephra layers. In those cores with visible tephra, we are also testing the possibility of using major element concentrations from Itrax scans to make preliminary identifications of tephra layers through their elemental fingerprints. The Itrax generated plots are tested for accuracy by comparing them against conventional electron microprobe analyses of traditionally extracted tephra shards. Humification analyses reflect the level of decomposition of an organic deposit which in itself signals changes in evaporation/precipitation and temperature regimes, and by extension, paleo-climate. At present humification is measured through leaching of samples and the use of a colorimeter. We are developing the use of the Itrax to capture major changes in humification by using the ratio of coherent to incoherent scattering

New insights into the genetic etiology of Alzheimer's disease and related dementias

Characterization of the genetic landscape of Alzheimer’s disease (AD) and related dementias (ADD) provides a unique opportunity for a better understanding of the associated pathophysiological processes. We performed a two-stage genome-wide association study totaling 111,326 clinically diagnosed/‘proxy’ AD cases and 677,663 controls. We found 75 risk loci, of which 42 were new at the time of analysis. Pathway enrichment analyses confirmed the involvement of amyloid/tau pathways and highlighted microglia implication. Gene prioritization in the new loci identified 31 genes that were suggestive of new genetically associated processes, including the tumor necrosis factor alpha pathway through the linear ubiquitin chain assembly complex. We also built a new genetic risk score associated with the risk of future AD/dementia or progression from mild cognitive impairment to AD/dementia. The improvement in prediction led to a 1.6- to 1.9-fold increase in AD risk from the lowest to the highest decile, in addition to effects of age and the APOE ε4 allele

New insights into the genetic etiology of Alzheimer's disease and related dementias

Characterization of the genetic landscape of Alzheimer’s disease (AD) and related dementias (ADD) provides a unique opportunity for a better understanding of the associated pathophysiological processes. We performed a two-stage genome-wide association study totaling 111,326 clinically diagnosed/‘proxy’ AD cases and 677,663 controls. We found 75 risk loci, of which 42 were new at the time of analysis. Pathway enrichment analyses confirmed the involvement of amyloid/tau pathways and highlighted microglia implication. Gene prioritization in the new loci identified 31 genes that were suggestive of new genetically associated processes, including the tumor necrosis factor alpha pathway through the linear ubiquitin chain assembly complex. We also built a new genetic risk score associated with the risk of future AD/dementia or progression from mild cognitive impairment to AD/dementia. The improvement in prediction led to a 1.6- to 1.9-fold increase in AD risk from the lowest to the highest decile, in addition to effects of age and the APOE ε4 allele

New insights into the genetic etiology of Alzheimer's disease and related dementias.

Characterization of the genetic landscape of Alzheimer's disease (AD) and related dementias (ADD) provides a unique opportunity for a better understanding of the associated pathophysiological processes. We performed a two-stage genome-wide association study totaling 111,326 clinically diagnosed/'proxy' AD cases and 677,663 controls. We found 75 risk loci, of which 42 were new at the time of analysis. Pathway enrichment analyses confirmed the involvement of amyloid/tau pathways and highlighted microglia implication. Gene prioritization in the new loci identified 31 genes that were suggestive of new genetically associated processes, including the tumor necrosis factor alpha pathway through the linear ubiquitin chain assembly complex. We also built a new genetic risk score associated with the risk of future AD/dementia or progression from mild cognitive impairment to AD/dementia. The improvement in prediction led to a 1.6- to 1.9-fold increase in AD risk from the lowest to the highest decile, in addition to effects of age and the APOE ε4 allele