An important role of heparan sulfate proteoglycan (Perlecan) in a model system for the deposition and persistence of fibrillar A beta-amyloid in rat brain.
A consistent rat model for the study of the consequences of congophilic and fibrillar A beta-amyloid in brain has been developed. One hundred percent of animals receiving infusions of synthetic beta-amyloid protein (A beta 1-40) plus a specific heparan sulfate proteoglycan (HSPG) for 1 week or 7 weeks (following 2 week infusions) demonstrated Congo red and thioflavin S-positive deposits adjacent to the infusion site. Extracellular amyloid fibrils were identified by electron microscopy and were immunogold decorated with A beta antibody. Significant increases in Congo red staining were observed in animals infused with A beta plus HSPG versus those infused with only A beta. Infusion of A beta alone was variable with respect to congophilic amyloid persistence, which occurred in 50% of animals and only when endogenous HSPGs accumulated at A beta deposition sites. By 7 weeks, only animals infused with A beta plus HSPG demonstrated compaction of the Congo red material from amorphous, wispy deposits (at 1 week) to stellate deposits resembling a Maltese cross. These spherical amyloid deposits were very similar to Congo red-stained amyloid plaques in human Alzheimer's disease brain, and in vitro data suggest that they were probably formed in vivo following interactions with endogenous brain components.
Snow
A D
AD
Department of Pathology, University of Washington, Seattle 98195.
Sekiguchi
R
R
Nochlin
D
D
Fraser
P
P
Kimata
K
K
Mizutani
A
A
Arai
M
M
Schreier
W A
WA
Morgan
D G
DG
D016229:Amyloid beta-Peptides / Q000008:administration & dosage / Q000378:metabolism*; D000818:Animals; D052160:Benzothiazoles; D001921:Brain / Q000378:metabolism* / Q000648:ultrastructure; D003224:Congo Red; D006025:Glycosaminoglycans / Q000032:analysis / Q000378:metabolism; D019812:Heparan Sulfate Proteoglycans; D006497:Heparan Sulfate / Q000008:administration & dosage / Q000302:isolation & purification / Q000378:metabolism*; D007150:Immunohistochemistry; D007263:Infusions, Parenteral; D008297:Male; D051379:Mice; D008854:Microscopy, Electron; D016253:Microscopy, Immunoelectron; D011509:Proteoglycans / Q000008:administration & dosage / Q000302:isolation & purification / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012513:Sarcoma, Experimental; D013238:Stereotaxic Techniques; D013844:Thiazoles; D013997:Time Factors
D016229:Amyloid beta-Peptides; D052160:Benzothiazoles; D003224:Congo Red; D006025:Glycosaminoglycans; D019812:Heparan Sulfate Proteoglycans; D006497:Heparan Sulfate; D011509:Proteoglycans; D013844:Thiazoles; C071927:perlecan; C009462:thioflavin T