TI  - Interaction of  <prot>transthyretin</prot>  with  <prot>amyloid beta-protein</prot> : binding and
      inhibition of amyloid formation.
PG  - 146-60; discussion 160-4
AB  - Aggregated <prot>amyloid beta-protein</prot> (<prot>A beta</prot>) is a key component of the amyloid
      depositions found in the brains of patients with Alzheimer's disease. In
      contrast, in cerebrospinal fluid (CSF), <prot>A beta</prot> is found in a soluble form.
      The analysis of complexes of <prot>A beta</prot> with CSF proteins in a KBr gradient
      revealed an association of <prot>A beta</prot> only with free proteins and not with
      lipoprotein particles.  <prot>Transthyretin</prot> (<prot>TTR</prot>) , a second major CSF protein,
      formed SDS-stable complexes with  <prot>A beta</prot>  and significantly decreased the
      rate of <prot>A beta</prot> fibril formation. In physiological buffers and CSF, <prot>TTR</prot>
      exclusively decreased the level of <prot>A beta</prot> pentamers. Endogenous  <prot>TTR</prot> - <prot>A beta</prot> 
      complexes were detected in human CSF by immunoprecipitation. Using
      site-directed mutagenesis and computer-assisted modelling, we identified
      amino acid residues on the surface of the  <prot>TTR</prot>  monomer that interact with  <prot>A
      beta</prot> . Specific <prot>TTR</prot> immunoreactivity was detected in multiple cortical
      neurons and astrocytes in the human brain. We propose that <prot>A beta</prot> binding
      proteins play a key role in the modulation of <prot>A beta</prot> aggregation and
      normally prevent amyloid formation in biological fluids and in the brain.
AD  - Department of Psychiatry, School of Medicine, State University of New York
