Alzheimer’s Disease Tau Consortium: How Do Soluble Tau Species Replicate

The tau molecule is normally inside neurons and is attached to the cell’s skeleton. Yet in Alzheimer’s disease, tau becomes misfolded, detaches from the cell’s skeleton and aggregates or clumps together to form a large skein of twisted filaments within the cell, called neurofibrillary tangles. When this happens in one neuron, it is probably a sign of stress. But in Alzheimer’s disease, the surrounding neurons to the first one, and those connected to it even far away in the brain, tend to also develop misfolded tau and neurofibrillary tangles. We propose to use new microscopic techniques to image tau when it misfolds and begins the process of detaching from the cell skeleton and aggregating in the cell body, as well as examining what kinds of tau can travel from cell to cell. We hope that learning the details of this process will teach us how to keep tau from spreading across the brain.