Sex-specific Associations of Gene Expression with Alzheimer's Disease Neuropathology and Ante-mortem Cognitive Performance.

The biological mechanisms underlying women's increased Alzheimer's disease (AD) prevalence remain undefined. Previous case/control studies have identified sex-biased molecular pathways, but sex-specific relationships between gene expression and AD endophenotypes, particularly sex chromosomes, are underexplored. With bulk transcriptomic data across 3 brain regions from 767 decedents, we investigated sex-specific associations between gene expression and post-mortem β-amyloid and tau as well as antemortem longitudinal cognition.

CSI-GEP: A GPU-based unsupervised machine learning approach for recovering gene expression programs in atlas-scale single-cell RNA-seq data.

Exploratory analysis of single-cell RNA sequencing (scRNA-seq) typically relies on hard clustering over two-dimensional projections like uniform manifold approximation and projection (UMAP). However, such methods can severely distort the data and have many arbitrary parameter choices. Methods that can model scRNA-seq data as non-discrete "gene expression programs" (GEPs) can better preserve the data's structure, but currently, they are often not scalable, not consistent across repeated runs, and lack an established method for choosing key parameters.

False-Negative Review from the Mammography Audit: Refining Breast Imaging Practice.

Annual review of false-negative (FN) mammograms is a mandatory and critical component of the Mammography Quality Standards Act (MQSA) annual mammography audit. FN review can help hone reading skills and improve the ability to detect cancers at mammography. Subtle architectural distortion, asymmetries (seen only on one view), small lesions, lesions with probably benign appearance (circumscribed regular borders), isolated microcalcifications, and skin thickening are the most common mammographic findings when the malignancy is visible at retrospective review of FN mammograms.

Vascular endothelial growth factor receptor-1 (FLT1) interactions with amyloid-beta in Alzheimer's disease: A putative biomarker of amyloid-induced vascular damage.

We have identified FLT1 as a protein that changes during Alzheimer's disease (AD) whereby higher brain protein levels are associated with more amyloid, more tau, and faster longitudinal cognitive decline. Given FLT1's role in angiogenesis and immune activation, we hypothesized that FLT1 is upregulated in response to amyloid pathology, driving a vascular-immune cascade resulting in neurodegeneration and cognitive decline. We sought to determine (1) if in vivo FLT1 levels (CSF and plasma) associate with biomarkers of AD neuropathology or differ between diagnostic staging in an aged cohort enriched for early disease, and (2) whether FLT1 expression interacts with amyloid on downstream outcomes, such as phosphorylated tau levels and cognitive performance.