The structure of an amyloid precursor protein/talin complex indicates a mechanical basis of Alzheimer's disease.

Misprocessing of amyloid precursor protein (APP) is one of the major causes of Alzheimer's disease. APP comprises a large extracellular region, a single transmembrane helix and a short cytoplasmic tail containing an NPxY motif (normally referred to as the YENPTY motif). Talins are synaptic scaffold proteins that connect the cytoskeletal machinery to the plasma membrane via binding NPxY motifs in the cytoplasmic tail of integrins.

New insights into the genetic etiology of Alzheimer's disease and related dementias.

Characterization of the genetic landscape of Alzheimer's disease (AD) and related dementias (ADD) provides a unique opportunity for a better understanding of the associated pathophysiological processes. We performed a two-stage genome-wide association study totaling 111,326 clinically diagnosed/'proxy' AD cases and 677,663 controls. We found 75 risk loci, of which 42 were new at the time of analysis.

The Alzheimer susceptibility gene BIN1 induces isoform-dependent neurotoxicity through early endosome defects.

The Bridging Integrator 1 (BIN1) gene is a major susceptibility gene for Alzheimer's disease (AD). Deciphering its pathophysiological role is challenging due to its numerous isoforms. Here we observed in Drosophila that human BIN1 isoform1 (BIN1iso1) overexpression, contrary to human BIN1 isoform8 (BIN1iso8) and human BIN1 isoform9 (BIN1iso9), induced an accumulation of endosomal vesicles and neurodegeneration.

Alternative glycosylation controls endoplasmic reticulum dynamics and tubular extension in mammalian cells.

The endoplasmic reticulum (ER) is a central eukaryotic organelle with a tubular network made of hairpin proteins linked by hydrolysis of guanosine triphosphate nucleotides. Among posttranslational modifications initiated at the ER level, glycosylation is the most common reaction. However, our understanding of the impact of glycosylation on the ER structure remains unclear.