Anti-Chol-1 Antigen, GQ1b[alpha], Antibodies Are Associated with Alzheimer's Disease

The interaction of amyloid [beta]-proteins (A[beta]) with membrane gangliosides has been reported to be an early event in A[beta] 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-1[alpha]; GQ1b[alpha]) 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, -GQ1b[alpha], 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-GQ1b[alpha] antibodies (IgM) were found in 90% (9/10) and 100% (6/6) in the sera of patients with AD and VD, respectively. Since GQ1b[alpha] is present in the cerebral cortex and hippocampus, the presence of anti-GQ1b[alpha] 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.