Histochemically reactive zinc in plaques of the Swedish mutant beta-amyloid precursor protein transgenic mice.
Endogenous metals such as zinc may contribute to beta-amyloid (Abeta) aggregation and hence the plaque formation. In the present study, we examined brains of four Swedish mutant amyloid precursor protein (APP) transgenic mice at 12 months of age for histochemically reactive zinc in the plaques. Here, we report that all the Congo red (+) mature plaques contained chelatable zinc, as demonstrated by staining with the zinc-specific fluorescent dye 6-methoxy-8-quinolyl-para-toluenesulfonamide (TSQ). On the other hand, Congo red (-) preamyloid Abeta deposits were not stained with TSQ. Interestingly, although cerebellum contained similar degree of preamyloid Abeta deposits as cerebral cortex, it was completely devoid of Congo red- or TSQ-stained mature plaques. Although zinc from plaques was only slowly and partially removed by a specific zinc remover, dithizone, treatment of brain sections with heparinase-III, which degrades heparan sulfate proteoglycan (HSPG), another major constituent of plaques, greatly fastened the zinc removal with dithizone. The present study has demonstrated the presence of histochemically reactive zinc in plaques, but not preamyloid Abeta deposits, of the Swedish mutant APP transgenic mice. Because preamyloid Abeta deposits fail to develop into congophilic plaques in cerebellum where synaptic vesicle zinc is deficient, the synaptic zinc may be a necessary element in the plaque formation. In holding zinc inside plaques, HSPG may contribute in addition to Abeta.
Lee
J Y
JY
National Creative Research Initiative Center for the Study of CNS Zinc and Department of Neurology, University of Ulsan College of Medicine, Seoul 138-736, Korea.
Mook-Jung
I
I
Koh
J Y
JY
D000634:Aminoquinolines; D016564:Amyloid beta-Protein Precursor / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D004396:Coloring Agents; D003224:Congo Red; D005456:Fluorescent Dyes; D007150:Immunohistochemistry; D051379:Mice; D008822:Mice, Transgenic; D008856:Microscopy, Fluorescence; D009154:Mutation; D058225:Plaque, Amyloid / Q000378:metabolism*; D014105:Tosyl Compounds; D015032:Zinc / Q000378:metabolism*
D000634:Aminoquinolines; D016564:Amyloid beta-Protein Precursor; D004396:Coloring Agents; D005456:Fluorescent Dyes; D014105:Tosyl Compounds; D003224:Congo Red; C061730:N-(6-methoxy-8-quinolyl)-4-toluenesulfonamide; D015032:Zinc