Ganglioside metabolism in a transgenic mouse model of Alzheimer's disease: expression of Chol-1a antigens in the brain

Hdl Handle:
http://hdl.handle.net/10675.2/600
Title:
Ganglioside metabolism in a transgenic mouse model of Alzheimer's disease: expression of Chol-1a antigens in the brain
Authors:
Ariga, Toshio; Yanagisawa, Makoto; Wakade, Chandramohan; Ando, Susumu; Buccafusco, Jerry J; McDonald, Michael P; Yu, Robert K.
Abstract:
The accumulation of Ab (amyloid b-protein) is one of the major pathological hallmarks in AD (Alzheimer’s disease). Gangliosides, sialic acid-containing glycosphingolipids enriched in the nervous system and frequently used as biomarkers associated with the biochemical pathology of neurological disorders, have been suggested to be involved in the initial aggregation of Ab. In the present study, we have examined ganglioside metabolism in the brain of a double- Tg (transgenic) mouse model of AD that co-expresses mouse/ human chimaeric APP (amyloid precursor protein) with the Swedish mutation and human presenilin-1 with a deletion of exon 9. Although accumulation of Ab was confirmed in the double-Tg mouse brains and sera, no statistically significant change was detected in the concentration and composition of major ganglio-N-tetraosyl-series gangliosides in the double-Tg brain. Most interestingly, Chol-1a antigens (cholinergic neuron-specific gangliosides), such as GT1aa and GQ1ba, which are minor species in the brain, were found to be increased in the double-Tg mouse brain. We interpret that the occurrence of these gangliosides may represent evidence for generation of cholinergic neurons in the AD brain, as a result of compensatory neurogenesis activated by the presence of Ab.
Citation:
ASN Neuro. 2010 Oct 4; 2(4):e00044
Issue Date:
4-Oct-2010
URI:
http://hdl.handle.net/10675.2/600
DOI:
10.1042/AN20100021
PubMed ID:
20930939
PubMed Central ID:
PMC2948441
Type:
Article
ISSN:
1759-0914
Appears in Collections:
Institute of Molecular Medicine and Genetics: Faculty Research and Presentations

Full metadata record

DC FieldValue Language
dc.contributor.authorAriga, Toshioen_US
dc.contributor.authorYanagisawa, Makotoen_US
dc.contributor.authorWakade, Chandramohanen_US
dc.contributor.authorAndo, Susumuen_US
dc.contributor.authorBuccafusco, Jerry Jen_US
dc.contributor.authorMcDonald, Michael Pen_US
dc.contributor.authorYu, Robert K.en_US
dc.date.accessioned2012-10-26T16:26:50Z-
dc.date.available2012-10-26T16:26:50Z-
dc.date.issued2010-10-4en_US
dc.identifier.citationASN Neuro. 2010 Oct 4; 2(4):e00044en_US
dc.identifier.issn1759-0914en_US
dc.identifier.pmid20930939en_US
dc.identifier.doi10.1042/AN20100021en_US
dc.identifier.urihttp://hdl.handle.net/10675.2/600-
dc.description.abstractThe accumulation of Ab (amyloid b-protein) is one of the major pathological hallmarks in AD (Alzheimer’s disease). Gangliosides, sialic acid-containing glycosphingolipids enriched in the nervous system and frequently used as biomarkers associated with the biochemical pathology of neurological disorders, have been suggested to be involved in the initial aggregation of Ab. In the present study, we have examined ganglioside metabolism in the brain of a double- Tg (transgenic) mouse model of AD that co-expresses mouse/ human chimaeric APP (amyloid precursor protein) with the Swedish mutation and human presenilin-1 with a deletion of exon 9. Although accumulation of Ab was confirmed in the double-Tg mouse brains and sera, no statistically significant change was detected in the concentration and composition of major ganglio-N-tetraosyl-series gangliosides in the double-Tg brain. Most interestingly, Chol-1a antigens (cholinergic neuron-specific gangliosides), such as GT1aa and GQ1ba, which are minor species in the brain, were found to be increased in the double-Tg mouse brain. We interpret that the occurrence of these gangliosides may represent evidence for generation of cholinergic neurons in the AD brain, as a result of compensatory neurogenesis activated by the presence of Ab.en_US
dc.rights© 2010 The Author(s).en_US
dc.subjectResearch Articleen_US
dc.subjectS3en_US
dc.subjectS1en_US
dc.subject.meshAlzheimer Diseaseen_US
dc.subject.meshAnimalsen_US
dc.subject.meshAntigens, Surfaceen_US
dc.subject.meshBrainen_US
dc.subject.meshCattleen_US
dc.subject.meshDisease Models, Animalen_US
dc.subject.meshGangliosidesen_US
dc.subject.meshHumansen_US
dc.subject.meshMiceen_US
dc.subject.meshMice, Transgenicen_US
dc.titleGanglioside metabolism in a transgenic mouse model of Alzheimer's disease: expression of Chol-1a antigens in the brainen_US
dc.typeArticleen_US
dc.identifier.pmcidPMC2948441en_US
dc.contributor.corporatenameInstitute of Molecular Medicine and Genetics-
dc.contributor.corporatenameDepartment of Pharmacology and Toxicology-
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