Affinity chromatography has, for many years, been at the research forefront as one of the simplest although highly versatile techniques capable of identifying biologically relevant
protein-
protein interactions. In the field of
amyloid disorders, the use of
ligands immobilized to a variety of affinity matrices was the method of choice to individualize
proteins with affinity for soluble circulating forms of
amyloid subunits. The methodology has also played an important role in the identification of
proteins that interact with different amyloidogenic
peptides and, as a result, are capable of modulating their physiological and pathological functions by altering solubility, aggregation propensity, and fibril formation proclivity. Along this line, classical studies conducted in the field of
Alzheimer's disease (AD) identified
clusterin as a major
binding protein to both circulating soluble Aβ as well as to the brain deposited counterpart. The affinity chromatography-based approach employed herein, individualized
clusterin as the major
protein capable of binding the
amyloid subunits associated with familial British and Danish
dementias, two non-Aβ neurodegenerative conditions also exhibiting cerebral
amyloid deposition and sharing striking similarities to AD. The data demonstrate that
clusterin binding ability to
amyloid molecules is not restricted to Aβ, suggesting a modulating effect on the aggregation/fibrillization propensity of the amyloidogenic
peptides that is consistent with its known chaperone activity.