Aβ oligomers peak in early stages of Alzheimer's disease preceding tau pathology.

Introduction: Soluble amyloid beta (Aβ) oligomers have been suggested as initiating Aβ related neuropathologic change in Alzheimer's disease (AD) but their quantitative distribution and chronological sequence within the AD continuum remain unclear.

Methods: A total of 526 participants in early clinical stages of AD and controls from a longitudinal cohort were neurobiologically classified for amyloid and tau pathology applying the AT(N) system. Aβ and tau oligomers in the quantified cerebrospinal fluid (CSF) were measured using surface-based fluorescence intensity distribution analysis (sFIDA) technology.

Machine Learning-Based Perivascular Space Volumetry in Alzheimer Disease.

Objectives: Impaired perivascular clearance has been suggested as a contributing factor to the pathogenesis of Alzheimer disease (AD). However, it remains unresolved when the anatomy of the perivascular space (PVS) is altered during AD progression. Therefore, this study investigates the association between PVS volume and AD progression in cognitively unimpaired (CU) individuals, both with and without subjective cognitive decline (SCD), and in those clinically diagnosed with mild cognitive impairment (MCI) or mild AD.

Performance evaluation of automated white matter hyperintensity segmentation algorithms in a multicenter cohort on cognitive impairment and dementia.

Background: White matter hyperintensities (WMH), a biomarker of small vessel disease, are often found in Alzheimer's disease (AD) and their advanced detection and quantification can be beneficial for research and clinical applications. To investigate WMH in large-scale multicenter studies on cognitive impairment and AD, appropriate automated WMH segmentation algorithms are required. This study aimed to compare the performance of segmentation tools and provide information on their application in multicenter research.

Apathy in patients with Alzheimer's disease is a cost-driving factor.

Background: Apathy is the most frequent neuropsychiatric symptom in patients with dementia of the Alzheimer's type (DAT). We analyzed the influence of apathy on the resource use of DAT patients and their caregivers.

Methods: Included were baseline data of 107 DAT patients from a randomized clinical trial on apathy treatment.

OXGR1 is a candidate disease gene for human calcium oxalate nephrolithiasis.

Purpose: Nephrolithiasis (NL) affects 1 in 11 individuals worldwide, leading to significant patient morbidity. NL is associated with nephrocalcinosis (NC), a risk factor for chronic kidney disease. Causative genetic variants are detected in 11% to 28% of NL and/or NC, suggesting that additional NL/NC-associated genetic loci await discovery.

Common variants in Alzheimer's disease and risk stratification by polygenic risk scores.

Genetic discoveries of Alzheimer's disease are the drivers of our understanding, and together with polygenetic risk stratification can contribute towards planning of feasible and efficient preventive and curative clinical trials. We first perform a large genetic association study by merging all available case-control datasets and by-proxy study results (discovery n = 409,435 and validation size n = 58,190). Here, we add six variants associated with Alzheimer's disease risk (near APP, CHRNE, PRKD3/NDUFAF7, PLCG2 and two exonic variants in the SHARPIN gene).

Bupropion for the Treatment of Apathy in Alzheimer Disease: A Randomized Clinical Trial.

Importance: Apathy is a frequent neuropsychiatric symptom in dementia of Alzheimer type and negatively affects the disease course and patients' and caregivers' quality of life. Effective treatment options are needed.

Objective: To examine the efficacy and safety of the dopamine and noradrenaline reuptake inhibitor bupropion in the treatment of apathy in patients with dementia of Alzheimer type.

Broadband multizone sound rendering by jointly optimizing the sound pressure and particle velocity.

In this paper, a recently proposed approach to multizone sound field synthesis, referred to as joint pressure and velocity matching (JPVM), is investigated analytically using a spherical harmonics representation of the sound field. The approach is motivated by the Kirchhoff-Helmholtz integral equation and aims at controlling the sound field inside the local listening zones by evoking the sound pressure and particle velocity on surrounding contours. Based on the findings of the modal analysis, an improved version of JPVM is proposed, which provides both better performance and lower complexity.

The spatial coherence of noise fields evoked by continuous source distributions.

In this work, analytic expressions for the spatial coherence of noise fields are derived in the modal domain with the aim of providing a sparse representation. For this purpose, the sound field in a region of interest is expressed in terms of a given pressure distribution on a virtual surrounding cylindrical or spherical surface. According to the Huygens-Fresnel principle, the sound pressure on this surface is represented by a continuous distribution of elementary line or point sources, where orthogonal basis functions characterize the spatial properties.

Glutamine metabolism of Corynebacterium glutamicum: role of the glutaminase GlsK.

Corynebacterium glutamicum is able to metabolize different nitrogen and carbon sources. In standard minimal media, ammonium and urea typically serve as nitrogen source and glucose or sucrose as carbon and energy source; however, amino acids might also play a role as nitrogen, carbon and energy source. In this study, the function of the putative glutaminase GlsK was investigated.

Promoter strength driving TetR determines the regulatory properties of Tet-controlled expression systems.

Bacteria frequently rely on transcription repressors and activators to alter gene expression patterns in response to changes in the surrounding environment. Tet repressor (TetR) is a paradigm transcription factor that senses the environmental state by binding small molecule effectors, the tetracyclines. However, recently isolated peptides that act as inducers of TetR after having been fused to the C-terminus of a carrier protein, suggest that TetR can also regulate gene expression in a signal-transduction pathway.

Body mass index is associated with biological CSF markers of core brain pathology of Alzheimer's disease.

Weight changes are common in aging and Alzheimer's disease (AD) and postmortem findings suggest a relation between lower body mass index (BMI) and increased AD brain pathology. In the current multicenter study, we tested whether lower BMI is associated with higher core AD brain pathology as assessed by cerebrospinal fluid (CSF)-based biological markers of AD in 751 living subjects: 308 patients with AD, 296 subjects with amnestic mild cognitive impairment (MCI), and 147 elderly healthy controls (HC). Based upon a priori cutoff values on CSF concentration of total tau and beta-amyloid (Aβ(1-42)), subjects were binarized into a group with abnormal CSF biomarker signature (CSF+) and those without (CSF-).