Characterization of high affinity binding between laminin and Alzheimer's disease amyloid precursor proteins.
BACKGROUND
In vivo amyloid formation apparently involves several extracellular matrix components that are usually found associated with basement membranes. These include laminin, heparan sulfate proteoglycan, collagen type IV, and entactin. These components have also been found in neuritic plaques. We have therefore been examining interactions between extracellular matrix components and the Alzheimer's amyloid precursors (AAPs).


METHODS
Binding interactions of laminin with AAP-695, -751, and -770 were examined using a solid phase enzyme-linked immunosorbent assay technique.


RESULTS
Objective, quantitative analyses of the laminin AAP-695, -751, and -770 binding data reveal two binding sites for laminin, with Kd values of 1 x 10(-10) M and 1 x 10(-8) M. Zinc and dithiothreitol profoundly stimulate laminin binding to AAPs. Furthermore, zinc fingers were found in the laminin amino acid sequences. Previous binding studies of AAPs with the basement membrane heparan sulfate proteoglycan revealed similar affinities. A particular order of addition of laminin and heparan sulfate proteoglycan to AAPs can be demonstrated.


CONCLUSIONS
These avid interactions with extracellular matrix proteins likely reflect normal functions of the AAPs and may be involved in nucleation events in Alzheimer-type amyloid formation.
Narindrasorasak
S
S
Department of Pathology, Queen's University, Syl and Molly Apps Research Center, Kingston General Hospital, Ontario, Canada.
Lowery
D E
DE
Altman
R A
RA
Gonzalez-DeWhitt
P A
PA
Greenberg
B D
BD
Kisilevsky
R
R
D000544:Alzheimer Disease / Q000378:metabolism*; D016564:Amyloid beta-Protein Precursor / Q000378:metabolism*; D001667:Binding, Competitive; D002413:Cations, Divalent / Q000494:pharmacology; D002712:Chlorides / Q000494:pharmacology; D003545:Cysteine / Q000378:metabolism; D004797:Enzyme-Linked Immunosorbent Assay; D005033:Ethylmaleimide / Q000494:pharmacology; D019812:Heparan Sulfate Proteoglycans; D006497:Heparan Sulfate / Q000378:metabolism; D006801:Humans; D007797:Laminin / Q000378:metabolism*; D011509:Proteoglycans / Q000378:metabolism; D015032:Zinc / Q000494:pharmacology; D017967:Zinc Compounds; D016335:Zinc Fingers
D016564:Amyloid beta-Protein Precursor; D002413:Cations, Divalent; D002712:Chlorides; D003545:Cysteine; D005033:Ethylmaleimide; D019812:Heparan Sulfate Proteoglycans; D006497:Heparan Sulfate; D007797:Laminin; D011509:Proteoglycans; D015032:Zinc; D017967:Zinc Compounds; C016837:zinc chloride