Preprints

Neural circuits undergo experience-dependent plasticity to form long-lasting memories. Excitatory projection neurons are considered to be the primary neuronal substrate for memory acquisition and storage. [...]

The axon initial segment (AIS) constitutes not only the site of action potential initiation, but also a hub for activity-dependent modulation of output generation. Recent studies shedding light on AIS function used predominantly post hoc approaches since no robust murine in vivo live reporters exist. [...]

Olfactory dysfunction is among the earliest signs of many age-related neurodegenerative diseases and has been associated with increased mortality in older adults; however, its genetic basis remains largely unknown.To identify the genetic loci associated with olfactory dysfunction in the general population.This genome-wide association study meta-analysis (GWMA) included participants of European ancestry (N = 22,730) enrolled in four different large population-based studies, followed by a multi-ancestry GWMA including participants of African ancestry (N = 1,030). The data analysis was performed from March 2023 through June 2024.Genome-wide single nucleotide polymorphisms.Olfactory dysfunction was the outcome and assessed using a 12-item smell identification test.GWMA revealed a novel genome-wide significant locus (tagged by rs11228623 at 11q12) associated with olfactory dysfunction. [...]

Objective: To assess whether severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection is associated with changes in plasma levels of neurofilament light chain (NfL), an extremely sensitive marker of neuroaxonal damage, in community-dwelling individuals.Setting: This study was embedded within the Rhineland Study, an ongoing community-based cohort study in Bonn, GermanyDesign: Cross-sectional nested case-control study.Participants: Participants were selected based on results from a previously conducted seroprevalence survey within the framework of the Rhineland Study. Cases were defined as those individuals who had had two positive confirmatory test results, including a recombinant spike-based immunofluorescence assay and a plaque reduction neutralization test (N=21). [...]

Background: Neurofilament light chain (NfL) levels in circulation have been established as a sensitive biomarker of neuro-axonal damage across a range of neurodegenerative disorders. Elucidation of the genetic architecture of blood NfL levels and its genetic correlation with neurological traits could therefore provide new insights into shared molecular mechanisms underlying neurodegenerative disorders.Methods: To identify the genetic variations underlying blood NfL levels, we conducted an ancestry-specific meta-analyses of genome-wide association studies (GWAS) based on 18,532 participants from 11 cohorts of European and 1142 participants (3 cohorts) of African-American ancestry. [...]

INTRODUCTION: Circulating microRNAs have been suggested as candidates for detecting and preventing subclinical cognitive dysfunction. However, replication of previous findings and identification of novel microRNAs associated with cognitive domains, including their relation to brain structure and the pathways they regulate, are still lacking.METHODS: We examined circulating microRNAs and microRNA co-expression clusters in relation to cognitive domains, structural MRI measures, and target gene expression in 2869 participants of a population-based cohort.RESULTS: Five previously identified and 10 novel microRNAs were associated with cognitive domains. [...]

Huntington disease (HD) is one of the most common repeat expansion disorders. Clinically, HD patients exhibit considerable visit-to-visit variability in symptoms and signs independent of measuring method or rater, yet neither the precise nature nor the determinants of this clinical variability are known. [...]

Background: The hypothalamus is the body’s principal homeostatic center. Emerging findings from animal studies suggest that the hypothalamus could also play a crucial role in the modulation of cognition. [...]

Recent technological advances enable genomics of individual cells, the building blocks of all living organisms. Single cell data characteristics differ from those of bulk data, which led to a plethora of new analytical strategies. [...]

Acute Myeloid Leukemia (AML) is a severe, mostly fatal hematopoietic malignancy. Despite nearly two decades of promising results using gene expression profiling, international recommendations for diagnosis and differential diagnosis of AML remain based on classical approaches including assessment of morphology, immunophenotyping, cytochemistry, and cytogenetics. [...]