DETECTION OF DISTINCT PATHOLOGICAL TAU CONFORMATIONS IN CSF OF PATIENTS WITH NEURODEGENERATIVE DISEASES

pharmacological agent used in the study is a proprietary and experimental compound provided by Neuropore Therapies Inc. (La Jolla, CA). Results: Short pre-incubation (w10min) of the compoundwith Ab(1-42) effectively prevented ion channel conductance (Figure C). However, the compound added along with A b(1-42) showed no change in ionic conductance (Figure B) vs. the control with A b(1-42) alone (Figure A), even at much higher compound concentrations. Conclusions: The need for pre-incubation, even at high compound concentrations, has led to two conclusions with regards to A b(1-42) toxicity: 1) the peptide inserts quickly into the membrane where it is shielded from the action of the compound. 2) A conformational change is likely induced during the incubation. A b forms b-sheet secondary structure and disruption of the b structure could prevent membrane insertion, channel formation, or induce a collapsed pore. Prior work with Ab containing a point substituted proline (a known b -sheet breaker) showed channel structure by AFMbut did not demonstrate ionic conductance. Taken together, the studies suggest that b -sheet structure is necessary for toxic conductance through A b channels.