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INTRODUCTIONTau species lacking truncation of the N-terminal region, including plasma N-terminal tau fragment 1 (NT1), have been previously associated with cognitive decline, neurodegeneration, and tau pathology in late-onset sporadic Alzheimer's disease (AD).METHODSHere, we examined cross-sectional and longitudinal plasma NT1 as a possible predictor of cognitive, clinical, and core AD biomarker trajectories in autosomal dominant AD (ADAD).RESULTSNT1 levels in ADAD mutation carriers (MC; n = 132) increased across the disease continuum, compared to non-carriers (NC; n = 75), becoming elevated about a decade prior to estimated symptom onset. Cross-sectional and longitudinal NT1 levels in MC were associated with clinical, cognitive, and biomarker changes. [...]

Although α-synuclein pathology is typically associated with Lewy body diseases and multiple systems atrophy, increasing evidence indicates that it also occurs in a group of lysosomal storage disorders termed sphingolipidoses caused by the incomplete degradation, and subsequent accumulation, of a class of lipids termed sphingolipids. Notably, a number of genes that cause sphingolipidoses are also risk genes for Lewy body diseases, suggesting aetiological links between these distinct disorders. [...]

Synucleinopathies are neurodegenerative diseases characterized by the presence of brain inclusions containing the pathologically aggregated protein α-synuclein. The development of a positron emission tomography tracer to detect aggregates of misfolded α-synuclein could revolutionize early diagnosis, disease monitoring, and the evaluation of therapeutic efficacy. [...]

Overexpression and exogenous administration of the anti-ageing hormone Klotho has been shown to enhance and promote adult hippocampal neurogenesis. However, whether locally produced Klotho from dentate gyrus neurons contributes to this process has remained unclear. [...]

Despite advances in mammography screening, some cancers remain undetected, prompting the evaluation of artificial intelligence (AI) as an independent third reader to reduce missed cancers.In this prospective study, women eligible for the German Mammography Screening were enrolled at six sites belonging to one screening unit between August 2023 and February 2024. Each mammogram underwent double reading and was independently analyzed using Transpara, an AI-based detection software. [...]

Combined oral contraceptive (COC) use has been associated with stress-like, metabolic, and inflammatory alterations. Previous studies demonstrated that metabolic changes were related to cortisol. [...]

Background/Objectives: Weight loss and hypermetabolism are negative prognostic factors in amyotrophic lateral sclerosis (ALS). Ketone bodies (β-hydroxybutyrate, βHB) as high-energy substrates may compensate for this energy deficit, since a ketogenic diet (KD) has been shown to increase survival and stabilize body weight in the SOD1 mouse model. [...]

Neuroinflammation is increasingly recognized as a key modulator of therapeutic response and adverse events in Alzheimer's disease (AD), especially during anti-amyloid-β (Aβ) monoclonal antibody (Aβ-mAb) treatment. We applied longitudinal translocator protein (TSPO) positron emission tomography (PET) to evaluate TSPO-associated neuroinflammatory responses to chronic Aβ-mAb therapy and their modulation by the peroxisome proliferator-activated receptor γ (PPARγ) agonist pioglitazone. [...]

Background: Recessive genetic variation and extended runs of homozygosity (ROHs) may contribute to the unexplained heritability of Parkinson's disease (PD), particularly in diverse and understudied populations.Objective: We conducted the first large-scale, multi-ancestral investigation of PD to examine the impact of genome-wide homozygosity on disease risk and age at onset (AAO). Using genotyping, imputed, and whole-genome sequencing data from 36,127 PD cases and 19,475 controls across nine ancestral populations from the Global Parkinson's Genetics Program, we aimed to identify novel regions of homozygosity contributing to PD heritability.Methods: We analyzed ROHs for total length (SROH), number (NROH), average length (AVROH), and genomic inbreeding coefficient (FROH). [...]

Deep brain stimulation (DBS) of the ventral intermediate nucleus (VIM) and caudal zona incerta is an established therapy for essential tremor (ET). Clinical outcomes depend on precise electrode placement and optimal stimulation parameters. [...]