Collagen XVIII: a novel heparan sulfate proteoglycan associated with vascular amyloid depositions and senile plaques in Alzheimer's disease brains.
Heparan sulfate proteoglycans (HSPGs) may play a role in the formation and persistence of senile plaques and neurofibrillary tangles in Alzheimer's disease brains. Recently, it has been demonstrated that the human extracellular matrix-associated molecule collagen XVIII is the first collagen carrying heparan sulfate side-chains. Two variants of collagen XVIII with both different signal peptides and N-terminal domains have been described and are referred to as the short and long form. To investigate the distribution of these variants we performed an immunohistochemical analysis by using specific well-characterized polyclonal antibodies. Anti-long huXVIII, a polyclonal antibody directed against the long variant of collagen XVIII, weakly stained large cortical and leptomeningeal vessels, whereas small cortical vessels remained unstained. Interestingly, all amyloid-laden vessels and classic senile plaques were strongly stained. Anti-all huXVIII, a polyclonal antibody directed against an epitope common to both collagen XVIII variants, intensely stained all types of cerebral blood vessels, cerebral amyloid angiopathy-affected vessels and classic senile plaques. Collagen XVIII expression was absent in neurofibrillary tangles. We conclude that collagen XVIII is a novel heparan sulfate proteoglycan associated with vascular A beta and classic senile plaques and that at least the long form of collagen XVIII accumulates in amyloid-laden vessels and classic senile plaques.
van Horssen
Jack
J
Department of Pathology, University Medical Center, Nijmegen, The Netherlands. j.vanhorssen@pathol.azn.nl
Wilhelmus
Micha M M
MM
Heljasvaara
Ritva
R
Pihlajaniemi
Taina
T
Wesseling
Pieter
P
de Waal
Robert M W
RM
Verbeek
Marcel M
MM
D000368:Aged; D000544:Alzheimer Disease / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D016229:Amyloid beta-Peptides / Q000378:metabolism; D000906:Antibodies; D000918:Antibody Specificity / Q000276:immunology; D002536:Cerebral Arteries / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D002540:Cerebral Cortex / Q000098:blood supply / Q000378:metabolism* / Q000473:pathology; D002550:Cerebral Veins / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D003094:Collagen / Q000276:immunology / Q000378:metabolism*; D043170:Collagen Type XVIII; D043169:Endostatins; D000939:Epitopes / Q000276:immunology; D005260:Female; D019812:Heparan Sulfate Proteoglycans / Q000276:immunology / Q000378:metabolism*; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008833:Microcirculation / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D010446:Peptide Fragments / Q000276:immunology / Q000378:metabolism*; D058225:Plaque, Amyloid / Q000378:metabolism* / Q000473:pathology; D016875:tau Proteins / Q000378:metabolism
D016229:Amyloid beta-Peptides; D000906:Antibodies; D043170:Collagen Type XVIII; D043169:Endostatins; D000939:Epitopes; D019812:Heparan Sulfate Proteoglycans; D010446:Peptide Fragments; D016875:tau Proteins; D003094:Collagen