Traffic Jam in Neurons Linked to Secretion of Alzheimer's Protein

Technology Networks reports that a new study in Science Translational Medicine determined that the secretion of tau protein is driven by tiny malfunctioning compartments — known as endosomes — within the brain's neurons, suggesting that they are commonly involved in the manifestation of Alzheimer's disease. Endosomal trafficking is disrupted in about 70 percent of study participants, including those only exhibiting the first symptoms of Alzheimer's. The researchers analyzed the spinal fluid of mice with the same endosomal trafficking dysfunction for proteins that differed from that in normal animals. Three proteins stood apart: two (n-APLP1 and n-CHL1) were cleaved proteins secreted by endosomes, while tau was the third. Analysis of human spinal fluid using new biomarkers of n-APLP1 and n-CHL1 and established biomarkers of tau uncovered a close relationship between the three proteins, suggesting that tau is normally secreted from the endosomal pathway. All three proteins are abnormally elevated in spinal fluid in approximately 70 percent of patients, even in those in the early "prodromal" stage of Alzheimer's disease. The authors are testing compounds to see if they can improve the endosome's trafficking function in animal models of Alzheimer's disease.