Tau protein, one of the main culprits implicated in Alzheimer’s disease, and the cell membrane are as thick as thieves. Tau and the membrane are, in fact, suspected of putting molecular events into motion that favor tau’s aggregation within neurons. These events are poorly understood, but their effects are not. When tau aggregates, neurons’ transport systems disintegrate, essential nutrients can’t move through, and the cells begin to die, affecting the brain’s functions and giving rise to the disease’s symptoms.
To better understand how the interplay between tau and lipid membranes can lead to the loss of neurons seen in Alzheimer’s disease, scientists based at Ecole Polytechnique Fédérale de Lausanne (EPFL) and Rockefeller University have studied how individual tau proteins interact with and disrupt the cell membrane of neurons. The scientists have found that tau’s disruption of the cell membrane gives rise to highly stable complexes. These complexes, the scientists report, consist of several tau proteins as well as fat molecules (phospholipids) from the membrane.
Details appeared of this work appeared November 22 in the journal Nature Communications, in an article entitled “Discovery and Characterization of Stable and Toxic Tau/Phospholipid Oligomeric Complexes.” The article shows that these complexes are more readily taken up by neurons compared to the fibril form of the protein, and induce toxicity in primary neurons of the hippocampus in vitro.
“These complexes…are detected by MC-1, an antibody recognizing pathological Tau conformations,” wrote the article’s authors. “The core of these complexes is comprised of the PHF6* [paired helical filament 6*] and PHF6 hexapeptide motifs, the latter in a β-strand conformation.”
The hippocampus is where memory is processed, and loss of hippocampal neurons is a classic symptom of Alzheimer’s disease. The complexes were detectable with MC-1, which is used as a standard for detecting pathological conformations of tau, meaning that they share some features of the pathological form of the protein.
Alzheimer’s Study Disentangles Tau–Membrane Interactions Linked with Tau Aggregation
