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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. [...]

Parkinson disease (PD)-associated mutations in the LRRK2 gene hyperactivate LRRK2 kinase activity, leading to increased phosphorylation of a subset of RAB GTPases, which are master regulators of intracellular trafficking. In neurons, processive retrograde transport of autophagosomes is essential for autophagosome maturation and effective degradation of autophagosomal cargo in the axon. [...]

Multiple system atrophy (MSA) and Parkinson's disease (PD) are both α-synucleinopathies with distinct pathological features and disease courses. MSA is characterized by more extensive white matter damage and widespread cortical and subcortical cholinergic systems degeneration than PD. [...]

Protein homeostasis is essential for maintaining normal cellular function. However, protein homeostasis efficiency declines with age, leading to the accumulation of aberrant protein structures associated with neurodegenerative diseases such as Parkinson's disease (PD). [...]

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. [...]