Co-incubation of an
amyloid protein with sulfated macromolecules as a method for the formation of
amyloid plaques. The
amyloid protein may be the beta-amyloid
protein or the prion protein or the like. Amyoid plaque formation in one embodiment proceeds
in vitro and desireably produces amyloid plaques that
stain with
Congo red and demonstrate a maltese-cross pattern when viewed under polarized light. The method also produces amyloid plaques that demonstrate an "amyloid star" appearance when viewed by
transmission electron microscopy. Sulfated macromolecules include a sulfated
proteoglycan selected from the group consisting of perlecan, ~220
kilodalton heparan sulfate proteoglyean,
glypican, cerebroglycan,
aggrecan, synaptoglycan (SV2PG), syndecan, N-syndecan (also known as syndecan-3), syndecan-1, syndecan-4, neurocan, phosphacan,
decorin, biglycan, versican, amphiglycan, lumican, PG-M, PG-M (3),
agrin, betaglycan, claustrin, brevican, appican, epican, neuroglycan-C, and fragments thereof. Thw sulfated
macromolecule may be a
sulfated glycosaminoglycan selected from the group consisting of
heparin,
heparan sulfate,
dermatan sulfate,
chondroitin sulfate,
keratan sulfate, and fragments thereof. An
in vivo assay is also presented for selecting a candidate therapeutic agent for inhibiting or disrupting amyloid plaque deposition or persistence. The
assay includes a) pre-forming congophilic maltese-cross amyloid plaques
in vitro following incubation of an amyloid protein and a selected sulfated
macromolecule, b) using a first cannula and
osmotic pump to continuously infuse for a selected duration the pre-formed congophilic maltese-cross amyloid plaques into a tissue or organ, c) changing the first cannulae and
osmotic pump with a second cannulae and
osmotic pump to administer the candidate therapeutic, and d) detecting the candidate therapeutic's ability to disrupt, reduce, or eliminate congophilic maltese-cross amyloid plaque deposition / persistence in the tissue or organ.