Anti-Chol-1 Antigen, GQ1bα, Antibodies Are Associated with Alzheimer's Disease

Toshio Ariga, Masaru Kubota, Makoto Nakane, Kenji Oguro, Robert K Yu, Susumu Ando

Research output: Contribution to journalArticle

6 Citations (Scopus)

Abstract

The interaction of amyloid β-proteins (Aβ) with membrane gangliosides has been reported to be an early event in Aβ fibril formation in Alzheimer's disease (AD). Neuronal degeneration in AD has been postulated to be associated with the presence of anti-ganglioside antibodies in patient sera. Using an enzyme-linked immunosorbent assay (ELISA) and high-performance thin-layer chromatography (HPTLC) immunostaining, sera from 27 individuals (10 with AD, 6 with vascular dementia (VD), and 11 non-demented age-matched pathological controls) were examined in order to detect anti-glycosphingolipid (GSL) antibodies, including anti-cholinergic-specific antigen (Chol-1α; GQ1bα) antibodies. All sera had natural antibodies against ganglio-N-tetraosyl gangliosides (brain-type gangliosides). However, sera of demented patients with AD and VD had significantly higher titers of anti-GSL antibodies than those in age-matched pathological controls. Although most serum antibodies, including anti- GM1, -GT1b, -GQ1b, -GQ1bα, were of the IgM type, the presence of the IgG type antibodies was also significantly elevated in the sera of demented patients with AD. Anti-GT1b antibodies of the IgG type were elevated in AD (90%, 9 of 10 cases) and VD (100%), respectively. Most surprisingly, anti-GQ1bα antibodies (IgM) were found in 90% (9/10) and 100% (6/6) in the sera of patients with AD and VD, respectively. Since GQ1bα is present in the cerebral cortex and hippocampus, the presence of anti-GQ1bα antibodies may play an important role in disrupting cholinergic synaptic transmission and may participate in the pathogenesis of dementia. We conclude that elevated anti-GSL antibody titers may be useful as an aid for clinical diagnosis of those dementias.

Original languageEnglish (US)
Article numbere63326
JournalPloS one
Volume8
Issue number5
DOIs
StatePublished - May 23 2013

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Alzheimer disease
Anti-Idiotypic Antibodies
Alzheimer Disease
antigens
dementia
Vascular Dementia
antibodies
Antibodies
Gangliosides
Glycosphingolipids
gangliosides
Serum
glycosphingolipids
blood vessels
Immunoglobulin M
Dementia
cholinergic agents
Immunoglobulin G
Serum Amyloid A Protein
chol-1 antigen

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)

Cite this

Anti-Chol-1 Antigen, GQ1bα, Antibodies Are Associated with Alzheimer's Disease. / Ariga, Toshio; Kubota, Masaru; Nakane, Makoto; Oguro, Kenji; Yu, Robert K; Ando, Susumu.

In: PloS one, Vol. 8, No. 5, e63326, 23.05.2013.

Research output: Contribution to journalArticle

Ariga, Toshio ; Kubota, Masaru ; Nakane, Makoto ; Oguro, Kenji ; Yu, Robert K ; Ando, Susumu. / Anti-Chol-1 Antigen, GQ1bα, Antibodies Are Associated with Alzheimer's Disease. In: PloS one. 2013 ; Vol. 8, No. 5.
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abstract = "The interaction of amyloid β-proteins (Aβ) with membrane gangliosides has been reported to be an early event in Aβ fibril formation in Alzheimer's disease (AD). Neuronal degeneration in AD has been postulated to be associated with the presence of anti-ganglioside antibodies in patient sera. Using an enzyme-linked immunosorbent assay (ELISA) and high-performance thin-layer chromatography (HPTLC) immunostaining, sera from 27 individuals (10 with AD, 6 with vascular dementia (VD), and 11 non-demented age-matched pathological controls) were examined in order to detect anti-glycosphingolipid (GSL) antibodies, including anti-cholinergic-specific antigen (Chol-1α; GQ1bα) antibodies. All sera had natural antibodies against ganglio-N-tetraosyl gangliosides (brain-type gangliosides). However, sera of demented patients with AD and VD had significantly higher titers of anti-GSL antibodies than those in age-matched pathological controls. Although most serum antibodies, including anti- GM1, -GT1b, -GQ1b, -GQ1bα, were of the IgM type, the presence of the IgG type antibodies was also significantly elevated in the sera of demented patients with AD. Anti-GT1b antibodies of the IgG type were elevated in AD (90{\%}, 9 of 10 cases) and VD (100{\%}), respectively. Most surprisingly, anti-GQ1bα antibodies (IgM) were found in 90{\%} (9/10) and 100{\%} (6/6) in the sera of patients with AD and VD, respectively. Since GQ1bα is present in the cerebral cortex and hippocampus, the presence of anti-GQ1bα antibodies may play an important role in disrupting cholinergic synaptic transmission and may participate in the pathogenesis of dementia. We conclude that elevated anti-GSL antibody titers may be useful as an aid for clinical diagnosis of those dementias.",
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