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P1‐121: DETECTION OF DISTINCT PATHOLOGICAL TAU CONFORMATIONS IN CSF OF PATIENTS WITH NEURODEGENERATIVE DISEASES
Author(s) -
Colby David,
Morozova Olga
Publication year - 2014
Publication title -
alzheimer's and dementia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 6.713
H-Index - 118
eISSN - 1552-5279
pISSN - 1552-5260
DOI - 10.1016/j.jalz.2014.05.358
Subject(s) - progressive supranuclear palsy , corticobasal degeneration , tau protein , chemistry , amyloid (mycology) , neurodegeneration , amyloid β , protein folding , circular dichroism , pathogenesis , biochemistry , biophysics , alzheimer's disease , pathology , disease , biology , medicine , inorganic chemistry
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.