Hot Off the Press: Autoantibodies to GM1 and GQ1bα are not Biological Markers of Alzheimer’s Disease
Uncovering novel biomarkers which lead to better diagnosis, prognosis and treatment is undoubtedly an important endeavor, but sometimes, finding what is not a biomarker may be worthwhile as well. Gangliosides are complex ceramide-glycosphingolipids known to play important roles in neuronal development. The GM1 ganglioside binds to β-amyloid and prevents β-sheet conformational changes (Yanagisawa et al., 1995), while GQ1bα and GT1aα are cholinergic neuron-specific gangliosides found to be increased in murine AD models (Ariga et al. 2010; Ariga et al. 2013a). Antibodies to gangliosides have been detected in AD, but the differences compared to controls were too low to be useful for diagnosis (Chapman et al. 1988). Other studies suffered from small patient numbers (n = 4, Hatzinfilippou et al. 2008), or low cut-off values resulting in low specificity (Ariga et al. 2013b).
In this study led by Prof. Nobuhiro Yuki, we measured serum levels of anti-ganglioside antibodies in patients with clinically diagnosed AD (n = 22) and vascular dementia (n = 14) and compared them to sera of patients with Guillain-Barré syndrome (GBS) and multifocal motor neuropathy (MMN), diseases where the antibodies are thought to be pathogenic; as well as to normal controls. We found that titers of IgG and IgM anti-GM1, anti-GQ1bα, and anti-GT1aα antibodies did not differ among AD, vascular dementia, and normal controls, and were remarkably lower than those in GBS and MMN. Our results suggest that the anti-ganglioside antibodies are unlikely to be pathogenic in AD or useful as biomarkers.
Miura Y, Miyaji K, Chai YL, Chen CL, Lai MK, Yuki N (This paper).
Ariga T, Yanagisawa M, Wakade C, Ando S, Buccafusco JJ, McDonald MP, Yu RK (2010) Ganglioside metabolism in a transgenic mouse model of Alzheimer’s disease: Expression of Chol-1α antigens in the brain. ASN Neuro 2: e00044.
Ariga T, ItokazuY, McDonald MP, Hirabayashi Y, Ando S, Yu RK (2013a) Brain gangliosides of a transgenic mouse model of Alzheimer’s disease with deficiency in GD3-synthase: Expression of elevated levels of a cholinergic-specific ganglioside, GT1aα. ASN Neuro 5: 141-148.
Ariga T, Kubota M, Nakane M, Oguro K, Yu RK, Ando S (2013b) Anti-Chol-1 antigen, GQ1bα, antibodies are associated with Alzheimer’s disease. PLoS One 8: e63326.
Chapman J, Sela BA, Wertman E, Michaelson DM (1988) Antibodies to ganglioside GM1 in patients with Alzheimer’s disease. Neurosci Lett 86: 235-240.
Hatzifilippou E, Koutsouraki E, Banaki T, Traka M, Costa VG, Baloyannis SJ (2008) Antibodies against GM1 in demented patients. Am J Alzheimers Dis Other Demen 23: 274-279.
Yanagisawa K, Odaka A, Suzuki N, Ihara Y (1995) GM1 ganglioside-bound amyloid beta-protein (Aβ): A possible form of preamyloid in Alzheimer’s disease. Nat Med 1: 1062-1066.