Presence of hydroxysteroid dehydrogenase type 10 in amyloid plaques (APs) of Hsiao's APP-Sw transgenic mouse brains, but absence in APs of Alzheimer's disease brains.
This immunocytochemical study using two anti-amyloid beta-protein (Abeta) monoclonal antibodies, 4G8 and 6E10, revealed the presence of Abeta in both amyloid plaques (APs) and blood vessels of brains of Hsiao's APP-Sw transgenic mice (also known as Tg2576) and human Alzheimer's disease (AD) brains. Further study using both monoclonal (5F3) and polyclonal (R-228) antibodies to hydroxysteroid dehydrogenase type 10 (HSD-10) [formerly called SCHAD (short-chain L-3-hydroxyacyl-CoA dehydrogenase); also called ERAB (endoplasmic-reticulum-associated amyloid beta-peptide-binding protein)] indicated that HSD-10 was present in the APs of Tg2576 mice but was absent or immunocytochemically undetectable in the APs of AD brains. Our observations also revealed that HSD-10 was present in the blood vessels of both Tg2576 mice and AD brains. Immunogold electron microscopy also indicated that HSD-10 was present in the amyloid fibers (AFs), mitochondria, nuclear heterochromatin, and nucleolus of Tg2576 mouse brains but was absent in APs of AD brains. These results suggest that the human APP gene transferred to mice may induce overexpression of HSD-10 in mouse APs and in various other cellular components of mouse brains. It is also possible that the human APP gene responsible for HSD-10 deposition in APs of these Tg2576 mice brains is different from that of AD brains. Alternatively, the HSD-10 gene and APP gene may function independently in AD brains. Despite these differences, the Tg2576 mouse, as shown in this study, is a proper animal model for the study of AD and also for the investigation of HSD-10.
Wen
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New York State Institute for Basic Research in Developmental Disabilities, 1050 Forest Hill Road, Staten Island, NY 10314, USA. guang.wen@omr.state.ny.us
Yang
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SY
Kaczmarski
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He
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Pappas
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KS
D015094:3-Hydroxyacyl CoA Dehydrogenases / Q000378:metabolism; D000544:Alzheimer Disease / Q000201:enzymology* / Q000235:genetics / Q000473:pathology; D016229:Amyloid beta-Peptides / Q000378:metabolism* / Q000648:ultrastructure; D000818:Animals; D001808:Blood Vessels / Q000201:enzymology / Q000648:ultrastructure; D001921:Brain / Q000201:enzymology / Q000473:pathology* / Q000648:ultrastructure; D006801:Humans; D006913:Hydroxysteroid Dehydrogenases / Q000378:metabolism*; D007150:Immunohistochemistry; D051379:Mice; D008822:Mice, Transgenic; D008854:Microscopy, Electron; D008928:Mitochondria / Q000201:enzymology / Q000473:pathology / Q000648:ultrastructure; D023421:Models, Animal; D058225:Plaque, Amyloid / Q000201:enzymology* / Q000235:genetics / Q000473:pathology / Q000648:ultrastructure
D016229:Amyloid beta-Peptides; D006913:Hydroxysteroid Dehydrogenases; D015094:3-Hydroxyacyl CoA Dehydrogenases; C108634:HSD17B10 protein, human