The protein Tau acts to stabilize microtubules but forma aberrant tangles in Alzheimer’s disease. This process appears to start from an expanded monomeric conformation.

Neurofibrillary tangles were discovered by Dr. A. Alzheimer as one of the two microscopic hallmarks of the disease that bears this name. These tangles are composed principally of the protein Tau, which normally binds and strengthens microtubules, misfolded into an amyloid structure. Although the structure of Tau amyloids are known to near atomic level precision, the process of their formation is less clear. Here, calorimetric and NMR spectroscopic studies from the IQFR’s department of Biological Physical Chemistry, as well as single molecule force spectroscopy results from an intercontinental research collaboration headed by the Cajal Institute, point to an expanded monomeric conformation as key for initiating Tau amyloidogenesis. Reference: Fernández-Ramírez MDC, Ng KK, Menéndez M, Laurents DV, Hervás R, Carrión-Vázquez M. (2022) “Expanded Conformations of Monomeric Tau Initiate Its Amyloidogenesis.” Angew Chem Int Ed Engl. e202209252. doi: 10.1002/anie.202209252. Figure caption. The protein Tau, symbolized by the bull, reveals its secrets after being subjected to single molecule force spectroscopy (crane worker), calorimetry (fire) and NMR spectroscopy (magnet) studies.