Documents in Process

Background:Advances in disease-modifying treatments and blood-based biomarkers for Alzheimer's disease (AD) have increased the importance of early diagnosis and dementia risk estimation before symptom onset. Autonomous decisions about AD risk estimation are complex and should align with individual needs and preferences. [...]

Background:The molecular basis for accelerated cognitive decline seen in Alzheimer's Disease (AD) cases presenting with cortical alpha-Synuclein co-pathology is not well understood. Mouse experiments have shown adverse interactions between tau (encoded by MAPT) and alpha-Synuclein (encoded by SNCA), but how this finding translates to humans from a genome-centered point of view remains unknown.Method:Whole genome sequencing was performed on 137 neuropathologically defined AD cases, 36 of which presented with neocortical alpha-Synuclein co-pathology (Braak stage 6). [...]

Background:Tau accumulation drives neurodegeneration and cognitive decline in Alzheimer's Disease (AD) and preclinical research suggests that tau spreads transsynaptically across connected neurons. We translated tau spreading models to human neuroimaging data, showing that tau pathology spreads from circumscribed epicenters to connected regions in AD, following the architecture of functional brain networks. [...]

Background:The integration of molecular imaging and multivariate connectivity approaches has emerged as a novel approach to gain insights into the underlying pathophysiology in neurodegenerative diseases. Metabolic connectivity, in particular, has already demonstrated disease-related pattern changes in both human and mammalian brains. [...]

Background:Alzheimer's disease (AD) strains healthcare systems in an aging population, emphasizing the need for continuous cognitive decline monitoring and its early detection. The Mini-Mental State Examination (MMSE) remains a widely used and cost-effective diagnostic tool, with efforts underway to adapt it for digital home-based assessments, enabling more frequent monitoring while minimizing patient burden and mobility. [...]

High-income countries experienced unprecedented gains in life expectancy throughout the twentieth century. However, recent evidence suggests that these gains have slowed, especially at older ages. [...]

The basal forebrain (BF), a key cholinergic hub, undergoes atrophy in Alzheimer's disease (AD), contributing to cognitive decline. However, its age-related differences and early vulnerability in autosomal dominant AD (ADAD) remain unclear.We studied 158 individuals from the Colombian Presenilin-1 (PSEN1) E280A kindred, including 80 carriers (60 cognitively unimpaired, 20 cognitively impaired). [...]

To present a new, fast MR imaging method for visualization and quantification of pulsatile displacement in brain tissue and fluid.The natural phase-contrast of non-balanced steady-state free precession combined with careful tuning of the intrinsic spoiler gradients is harnessed to measure displacement along specific physical directions. Efficient segmented 3D-EPI allows for whole brain coverage within TR = 0.15 s. [...]

Studying the dynamic role of microglia in brain development and neurodegenerative diseases requires models that closely resemble the human brain environment. While human induced pluripotent stem cell (iPSC)-derived organoids (hORGs) effectively reproduce key neuronal and certain glial cell types, modeling human microglia in vitro remains challenging. [...]

The extracellular matrix protein reelin is well known for orchestrating radial migration of cortical neurons during embryonic cortical development. While in the reeler mutant mouse, lacking reelin expression, radially migrating neurons are malpositioned and display dendritic malformations, no such deficits were found after conditionally induced reelin deficiency (RelncKO) in the hippocampus of mice aged two months. [...]