Experimental deposition of Alzheimer amyloid beta-protein in canine leptomeningeal vessels.
To study the pathogenesis of cerebral amyloid angiopathy (CAA), organ cultures of canine leptomeninges were incubated with fluorescein-conjugated amyloid beta-protein (FA beta, residues 1-40; 10 nM to 200 microM). Fluorescence microscopy showed focal and dose-dependent FA beta binding to blood vessels affected by CAA at FA beta-concentrations as low as 10 nM. The new A beta deposits appeared to be extracellular and were localized to the middle and outer layers of leptomeningeal arterioles. FA beta partially co-localized with apolipoprotein E (ApoE) as revealed by confocal microscopy, suggesting that A beta in situ binds to ApoE. Young dogs or old dogs without CAA showed no deposition of FA beta. Our results indicate that after initiation of CAA pathology, physiological concentrations of soluble A beta are sufficient to sustain its further deposition and therefore the progression of CAA.
Department of Neurology, University of Düsseldorf, Germany.
R
R
Prior
D
D
D'Urso
R
R
Frank
I
I
Prikulis
G
G
Pavlakovic
D000544:Alzheimer Disease / Q000378:metabolism*; D000595:Amino Acid Sequence; D016229:Amyloid beta-Peptides / Q000378:metabolism*; D000818:Animals; D001099:Arachnoid / Q000098:blood supply*; D003470:Culture Media; D004285:Dogs; D008856:Microscopy, Fluorescence; D008969:Molecular Sequence Data; D009924:Organ Culture Techniques; D010841:Pia Mater / Q000098:blood supply*; D011485:Protein Binding; D012995:Solubility
D016229:Amyloid beta-Peptides; D003470:Culture Media