Benchmarking of a multi-biomarker low-volume panel for Alzheimer's disease and related dementia research.

Introduction: In the research setting, obtaining accurate established biomarker measurements and maximizing use of the precious samples is key. Accurate technologies are available for Alzheimer's disease (AD), but no platform can measure all the established and emerging biomarkers in one run. The NUcleic acid Linked Immuno-Sandwich Assay (NULISA) is a technology that requires 15 µL of sample to measure more than 100 analytes.

Enhancing Gout Diagnosis with Deep Learning in Dual-energy Computed Tomography: A Retrospective Analysis of Crystal and Artifact Differentiation.

Objectives: To evaluate whether the application of deep learning (DL) could achieve high diagnostic accuracy in differentiating between green colour coding, indicative of tophi, and clumpy artifacts observed in dual-energy computed tomography (DECT) scans.

Methods: A comprehensive analysis of 18 704 regions of interest (ROIs) extracted from green foci in DECT scans obtained from 47 patients with gout and 27 gout-free controls was performed. The ROIs were categorized into three size groups: small, medium, and large.

Proteogenomic analysis of human cerebrospinal fluid identifies neurologically relevant regulation and implicates causal proteins for Alzheimer's disease.

The integration of quantitative trait loci (QTLs) with disease genome-wide association studies (GWASs) has proven successful in prioritizing candidate genes at disease-associated loci. QTL mapping has been focused on multi-tissue expression QTLs or plasma protein QTLs (pQTLs). We generated a cerebrospinal fluid (CSF) pQTL atlas by measuring 6,361 proteins in 3,506 samples.

Probing Nanoscale Charge Transport Mechanisms in Quasi-2D Halide Perovskites for Photovoltaic Applications.

Quasi-2D layered halide perovskites (quasi-2DLPs) have emerged as promising materials for photovoltaic (PV) applications owing to their advantageous bandgap for absorbing visible light and the improved stability they enable. Their charge transport mechanism is heavily influenced by the grain orientation of their crystals as well as their nanostructures, such as grain boundaries (GBs) and edge states─the formation of which is inevitable in polycrystalline quasi-2DLP thin films. Despite their importance, the impact of these features on charge transport remains unexplored.

CSF proteomics identifies early changes in autosomal dominant Alzheimer's disease.

In this high-throughput proteomic study of autosomal dominant Alzheimer's disease (ADAD), we sought to identify early biomarkers in cerebrospinal fluid (CSF) for disease monitoring and treatment strategies. We examined CSF proteins in 286 mutation carriers (MCs) and 177 non-carriers (NCs). The developed multi-layer regression model distinguished proteins with different pseudo-trajectories between these groups.

Scanning Probe Microscopy of Halide Perovskite Solar Cells.

Scanning probe microscopy (SPM) has enabled significant new insights into the nanoscale and microscale properties of solar cell materials and underlying working principles of photovoltaic and optoelectronic technology. Various SPM modes, including atomic force microscopy, Kelvin probe force microscopy, conductive atomic force microscopy, piezoresponse force microscopy, and scanning near-field optical microscopy, can be used for the investigation of electrical, optical and chemical properties of associated functional materials. A large body of work has improved the understanding of solar cell device processing and synthesis in close synergy with SPM investigations in recent years.

European and African-specific plasma protein-QTL and metabolite-QTL analyses identify ancestry-specific T2D effector proteins and metabolites.

Initially focused on the European population, multiple genome-wide association studies (GWAS) of complex diseases, such as type-2 diabetes (T2D), have now extended to other populations. However, to date, few ancestry-matched omics datasets have been generated or further integrated with the disease GWAS to nominate the key genes and/or molecular traits underlying the disease risk loci. In this study, we generated and integrated plasma proteomics and metabolomics with array-based genotype datasets of European (EUR) and African (AFR) ancestries to identify ancestry-specific muti-omics quantitative trait loci (QTLs).

Ubiquitin-Proteasome System in the Different Stages of Dominantly Inherited Alzheimer's Disease.

This study explored the role of the ubiquitin-proteasome system (UPS) in dominantly inherited Alzheimer's disease (DIAD) by examining changes in cerebrospinal fluid (CSF) levels of UPS proteins along with disease progression, AD imaging biomarkers (PiB PET, tau PET), neurodegeneration imaging measures (MRI, FDG PET), and Clinical Dementia Rating (CDR). Using the SOMAscan assay, we detected subtle increases in specific ubiquitin enzymes associated with proteostasis in mutation carriers (MCs) up to two decades before the estimated symptom onset. This was followed by more pronounced elevations of UPS-activating enzymes, including E2 and E3 proteins, and ubiquitin-related modifiers.

A genetic and proteomic comparison of key AD biomarkers across tissues.

Introduction: Plasma has been proposed as an alternative to cerebrospinal fluid (CSF) for measuring Alzheimer's disease (AD) biomarkers, but no studies have analyzed in detail which biofluid is more informative for genetics studies of AD.

Method: Eleven proteins associated with AD (α-synuclein, apolipoprotein E [apoE], CLU, GFAP, GRN, NfL, NRGN, SNAP-25, TREM2, VILIP-1, YKL-40) were assessed in plasma (n = 2317) and CSF (n = 3107). Both plasma and CSF genome-wide association study (GWAS) analyses were performed for each protein, followed by functional annotation.

Benchmarking of a multi-biomarker low-volume panel for Alzheimer's Disease and related dementia research.

Alzheimer's Disease (AD) biomarker measurement is key to aid in the diagnosis and prognosis of the disease. In the research setting, participant recruitment and retention and optimization of sample use, is one of the main challenges that observational studies face. Thus, obtaining accurate established biomarker measurements for stratification and maximizing use of the precious samples is key.

Sex and aging signatures of proteomics in human cerebrospinal fluid identify distinct clusters linked to neurodegeneration.

Sex and age are major risk factors for chronic diseases. Recent studies examining age-related molecular changes in plasma provided insights into age-related disease biology. Cerebrospinal fluid (CSF) proteomics can provide additional insights into brain aging and neurodegeneration.

An interpretable machine learning-based cerebrospinal fluid proteomics clock for predicting age reveals novel insights into brain aging.

Machine learning can be used to create "biologic clocks" that predict age. However, organs, tissues, and biofluids may age at different rates from the organism as a whole. We sought to understand how cerebrospinal fluid (CSF) changes with age to inform the development of brain aging-related disease mechanisms and identify potential anti-aging therapeutic targets.

Fostering Charge Carrier Transport and Absorber Growth Properties in CZTSSe Thin Films with an ALD-SnO Capping Layer.

The present study demonstrates that precursor passivation is an effective approach for improving the crystallization process and controlling the detrimental defect density in high-efficiency CuZnSn(S,Se) (CZTSSe) thin films. It is achieved by applying the atomic layer deposition (ALD) of the tin oxide (ALD-SnO) capping layer onto the precursor (Cu-Zn-Sn) thin films. The ALD-SnO capping layer was observed to facilitate the homogeneous growth of crystalline grains and mitigate defects prior to sulfo-selenization in CZTSSe thin films.

Post-GWAS multiomic functional investigation of the TNIP1 locus in Alzheimer's disease highlights a potential role for GPX3.

Introduction: Recent genome-wide association studies (GWAS) have reported a genetic association with Alzheimer's disease (AD) at the TNIP1/GPX3 locus, but the mechanism is unclear.

Methods: We used cerebrospinal fluid (CSF) proteomics data to test (n = 137) and replicate (n = 446) the association of glutathione peroxidase 3 (GPX3) with CSF biomarkers (including amyloid and tau) and the GWAS-implicated variants (rs34294852 and rs871269).

Results: CSF GPX3 levels decreased with amyloid and tau positivity (analysis of variance P = 1.

TOPMed imputed genomics enhances genomic atlas of the human proteome in brain, cerebrospinal fluid, and plasma.

Comprehensive expression quantitative trait loci studies have been instrumental for understanding tissue-specific gene regulation and pinpointing functional genes for disease-associated loci in a tissue-specific manner. Compared to gene expressions, proteins more directly affect various biological processes, often dysregulated in disease, and are important drug targets. We previously performed and identified tissue-specific protein quantitative trait loci in brain, cerebrospinal fluid, and plasma.

Blood-Based Proteomics for Adult-Onset Focal Dystonias.

Objectives: The adult-onset focal dystonias are characterized by over-active muscles leading to abnormal movements. For most cases, the etiology and pathogenesis remain unknown. In the current study, unbiased proteomics methods were used to identify potential changes in blood plasma proteins.

CSF biomarkers of immune activation and Alzheimer's disease for predicting cognitive impairment risk in the elderly.

The immune system substantially influences age-related cognitive decline and Alzheimer's disease (AD) progression, affected by genetic and environmental factors. In a Mayo Clinic Study of Aging cohort, we examined how risk factors like APOE genotype, age, and sex affect inflammatory molecules and AD biomarkers in cerebrospinal fluid (CSF). Among cognitively unimpaired individuals over 65 ( = 298), we measured 365 CSF inflammatory molecules, finding age, sex, and diabetes status predominantly influencing their levels.

CSF proteomic profiling with amyloid/tau positivity identifies distinctive sex-different alteration of multiple proteins involved in Alzheimer's disease.

In Alzheimer's disease (AD), the most common cause of dementia, females have higher prevalence and faster progression, but sex-specific molecular findings in AD are limited. Here, we comprehensively examined and validated 7,006 aptamers targeting 6,162 proteins in cerebral spinal fluid (CSF) from 2,077 amyloid/tau positive cases and controls to identify sex-specific proteomic signatures of AD. In discovery (N=1,766), we identified 330 male-specific and 121 female-specific proteomic alternations in CSF (FDR <0.