Basic Science and Pathogenesis.

Background: P-tau217 has emerged as a compelling alternative to long-established p-tau181 to accurately measure tau modifications in biofluids in response to brain Abeta and tau deposition in Alzheimer's disease (AD). Understanding the specificity and significance of p-tau217 changes over AD stages is critical to interpret its potential response to treatments against Abeta and tau aggregation.

Methods: We measured p-tau217 phosphorylation by mass spectrometry.

Basic Science and Pathogenesis.

Background: Structural and functional changes of the choroid plexus (ChP) have been reported in Alzheimer's disease (AD). Nonetheless, the role of the ChP in the pathogenesis of AD remains largely unknown. We aim to unravel the relationship between ChP functioning and core AD pathogenesis using a unique proteomic approach in mice and humans.

Clinical Manifestations.

Background: The ability to detect cognitive impairment from Alzheimer Disease (AD) in its earliest possible symptomatic stage is a highly desirable characteristic for neuropsychological measures. Because early cognitive changes are often subtle, measures with high sensitivity are of great importance. Variability in attention, often assessed using reaction time (RT) tasks, have been shown to discriminate between cognitively normal older individuals with and without positive AD biomarkers and is correlated with biological markers of neurodegeneration.

The human zinc-binding cysteine proteome.

Zinc is an essential micronutrient that regulates a wide range of physiological processes, most often through zinc binding to protein cysteine residues. Despite being critical for modulation of protein function, the cysteine sites in the majority of the human proteome that are subject to zinc binding remain undefined. Here, we develop ZnCPT, a deep and quantitative mapping of the zinc-binding cysteine proteome.

Clinical use of biomarkers in the era of Alzheimer's disease treatments.

With the advent of treatments that specifically target Alzheimer's disease brain pathology, biomarker tests will become an increasingly important part of the routine clinical evaluation of cognitive impairment and guide clinical decision making. Clinicians must ensure they are using accurate and well-validated biomarker tests and select the most appropriate testing modality for each patient based on individual and practical considerations. The interpretation of test results may be complex and depends on the pre-test probability and test-specific factors.

ADNI Biomarker Core: A review of progress since 2004 and future challenges.

Background: We describe the Alzheimer's Disease Neuroimaging Initiative (ADNI) Biomarker Core major activities from October 2004 to March 2024, including biobanking ADNI cerebrospinal fluid (CSF), plasma, and serum biofluid samples, biofluid analyses for Alzheimer's disease (AD) biomarkers in the Biomarker Core and various non-ADNI laboratories, and continuous assessments of pre-analytics.

Results: Validated immunoassay and mass spectrometry-based assays were performed in CSF with a shift to plasma, a more accessible biofluid, as qualified assays became available. Performance comparisons across different CSF and plasma AD biomarker measurement platforms have enriched substantially the ADNI participant database enabling method performance determinations for AD pathology detection and longitudinal assessments of disease progression.

Timing of changes in Alzheimer's disease plasma biomarkers as assessed by amyloid and tau PET clocks.

Plasma biomarkers for Alzheimer's disease (AD) are increasingly being used to assist in making an etiological diagnosis for cognitively impaired (CI) individuals or to identify cognitively unimpaired (CU) individuals with AD pathology who may be eligible for prevention trials. However, a better understanding of the timing of plasma biomarker changes is needed to optimize their use in clinical and research settings. The aim of this study was to evaluate the timing of change of key AD plasma biomarkers (Aβ42/Aβ40, p-tau217, p-tau181, GFAP and NfL) from six different companies, along with established AD biomarkers, using AD progression timelines based on amyloid and tau PET.

A comprehensive head-to-head comparison of key plasma phosphorylated tau 217 biomarker tests.

Plasma phosphorylated-tau 217 (p-tau217) is currently the most promising biomarker for reliable detection of Alzheimer's disease (AD) pathology. Various p-tau217 assays have been developed, but their relative performance is unclear. We compared key plasma p-tau217 tests using cross-sectional and longitudinal measures of amyloid-β (Aβ)-PET, tau-PET, and cognition as outcomes, and benchmarked them against cerebrospinal fluid (CSF) biomarker tests.

Self-stigma in alcohol dependence scale: development and validity of the short form.

Background: Self-stigma is associated with low self-esteem, high shame and reduced drinking-refusal self-efficacy in people with alcohol use disorder (AUD). The Self-Stigma in Alcohol-Dependence Scale-Short Form (SSAD-SF) was designed to enable a brief, but valid assessment of AUD self-stigma.

Methods: We reduced the 64-item SSAD, originally derived from 16 stereotypes towards people with AUD, by removing the most offensive items based on perspectives of people with lived experience.

Effectiveness of ex ante honesty oaths in reducing dishonesty depends on content.

Dishonest behaviours such as tax evasion impose significant societal costs. Ex ante honesty oaths-commitments to honesty before action-have been proposed as interventions to counteract dishonest behaviour, but the heterogeneity in findings across operationalizations calls their effectiveness into question. We tested 21 honesty oaths (including a baseline oath)-proposed, evaluated and selected by 44 expert researchers-and a no-oath condition in a megastudy involving 21,506 UK and US participants from Prolific.

Expanding the Clip-and-Cleave Concept: Approaching Enantioselective C-H Hydroxylations by Copper Imine Complexes Using O and HO as Oxidants.

Copper-mediated aromatic and aliphatic C-H hydroxylations using benign oxidants (O and HO) have been studied intensively in recent years to meet the growing demand for efficient and green C-H functionalizations. Herein, we report an enantioselective variant of the so-called clip-and-cleave concept for intramolecular ligand hydroxylations by the application of chiral diamines as directing groups. We tested the hydroxylation of cyclohexanone and 1-acetyladamantane under different oxidative conditions (Cu/O; Cu/HO; Cu/HO) in various solvents.

Protein NMR assignment by isotope pattern recognition.

The current standard method for amino acid signal identification in protein NMR spectra is sequential assignment using triple-resonance experiments. Good software and elaborate heuristics exist, but the process remains laboriously manual. Machine learning does help, but its training databases need millions of samples that cover all relevant physics and every kind of instrumental artifact.

Metabolipidomic changes induced by dermal nickel penetration determined in an ex vivo porcine ear skin model.

Rational: Nickel is one of humans' most prevalent triggers of allergic contact dermatitis. However, the underlying mechanisms of this allergy still need to be fully understood. One aspect that has yet to be explored is the direct impact of common metal allergens on the skin's metabolites and lipids composition.

Acquisition and generalization of emotional and neural responses to faces associated with negative and positive feedback behaviours.

Faces can acquire emotional meaning by learning to associate individuals with specific behaviors. Here, we investigated emotional evaluation and brain activations toward faces of persons who had given negative or positive evaluations to others. Furthermore, we investigated how emotional evaluations and brain activation generalize to perceptually similar faces.

Examining the alignment between subjective effort and objective force production.

Ratings of Perceived Exertion (RPE) are frequently used to prescribe exercise intensity. A central assumption of using RPE scales is that the subjective perception of effort maps onto objective performance in a consistent way. However, the degree and shape of how RPE aligns with objective performance is not fully understood.