Tags

Type your tag names separated by a space and hit enter

Antibodies against beta-amyloid reduce Abeta oligomers, glycogen synthase kinase-3beta activation and tau phosphorylation in vivo and in vitro.
J Neurosci Res. 2006 Feb 15; 83(3):374-84.JN

Abstract

Although active and passive immunization against the beta-amyloid peptide (Abeta) of amyloid plaque-bearing transgenic mice markedly reduces amyloid plaque deposition and improves cognition, the mechanisms of neuroprotection and impact on toxic oligomer species are not understood. We demonstrate that compared to control IgG2b, passive immunization with intracerebroventricular (icv) anti-Abeta (1-15) antibody into the AD HuAPPsw (Tg2576) transgenic mouse model reduced specific oligomeric forms of Abeta, including the dodecamers that correlate with cognitive decline. Interestingly, the reduction of soluble Abeta oligomers, but not insoluble Abeta, significantly correlated with reduced tau phosphorylation by glycogen synthase kinase-3beta (GSK-3beta), a major tau kinase implicated previously in mediating Abeta toxicity. A conformationally-directed antibody against amyloid oligomers (larger than tetramer) also reduced Abeta oligomer-induced activation of GSK3beta and protected human neuronal SH-SY5Y cells from Abeta oligomer-induced neurotoxicity, supporting a role for Abeta oligomers in human tau kinase activation. These data suggest that antibodies that are highly specific for toxic oligomer subspecies may reduce toxicity via reduction of GSK-3beta, which could be an important strategy for Alzheimer's disease (AD) therapeutics.

Authors+Show Affiliations

Department of Medicine, University of California, Los Angeles, California 91343, USA.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural

Language

eng

PubMed ID

16385556

Citation

Ma, Qiu-Lan, et al. "Antibodies Against Beta-amyloid Reduce Abeta Oligomers, Glycogen Synthase Kinase-3beta Activation and Tau Phosphorylation in Vivo and in Vitro." Journal of Neuroscience Research, vol. 83, no. 3, 2006, pp. 374-84.
Ma QL, Lim GP, Harris-White ME, et al. Antibodies against beta-amyloid reduce Abeta oligomers, glycogen synthase kinase-3beta activation and tau phosphorylation in vivo and in vitro. J Neurosci Res. 2006;83(3):374-84.
Ma, Q. L., Lim, G. P., Harris-White, M. E., Yang, F., Ambegaokar, S. S., Ubeda, O. J., Glabe, C. G., Teter, B., Frautschy, S. A., & Cole, G. M. (2006). Antibodies against beta-amyloid reduce Abeta oligomers, glycogen synthase kinase-3beta activation and tau phosphorylation in vivo and in vitro. Journal of Neuroscience Research, 83(3), 374-84.
Ma QL, et al. Antibodies Against Beta-amyloid Reduce Abeta Oligomers, Glycogen Synthase Kinase-3beta Activation and Tau Phosphorylation in Vivo and in Vitro. J Neurosci Res. 2006 Feb 15;83(3):374-84. PubMed PMID: 16385556.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Antibodies against beta-amyloid reduce Abeta oligomers, glycogen synthase kinase-3beta activation and tau phosphorylation in vivo and in vitro. AU - Ma,Qiu-Lan, AU - Lim,Giselle P, AU - Harris-White,Marni E, AU - Yang,Fusheng, AU - Ambegaokar,Surendra S, AU - Ubeda,Oliver J, AU - Glabe,Charles G, AU - Teter,Bruce, AU - Frautschy,Sally A, AU - Cole,Greg M, PY - 2005/12/31/pubmed PY - 2006/5/26/medline PY - 2005/12/31/entrez SP - 374 EP - 84 JF - Journal of neuroscience research JO - J. Neurosci. Res. VL - 83 IS - 3 N2 - Although active and passive immunization against the beta-amyloid peptide (Abeta) of amyloid plaque-bearing transgenic mice markedly reduces amyloid plaque deposition and improves cognition, the mechanisms of neuroprotection and impact on toxic oligomer species are not understood. We demonstrate that compared to control IgG2b, passive immunization with intracerebroventricular (icv) anti-Abeta (1-15) antibody into the AD HuAPPsw (Tg2576) transgenic mouse model reduced specific oligomeric forms of Abeta, including the dodecamers that correlate with cognitive decline. Interestingly, the reduction of soluble Abeta oligomers, but not insoluble Abeta, significantly correlated with reduced tau phosphorylation by glycogen synthase kinase-3beta (GSK-3beta), a major tau kinase implicated previously in mediating Abeta toxicity. A conformationally-directed antibody against amyloid oligomers (larger than tetramer) also reduced Abeta oligomer-induced activation of GSK3beta and protected human neuronal SH-SY5Y cells from Abeta oligomer-induced neurotoxicity, supporting a role for Abeta oligomers in human tau kinase activation. These data suggest that antibodies that are highly specific for toxic oligomer subspecies may reduce toxicity via reduction of GSK-3beta, which could be an important strategy for Alzheimer's disease (AD) therapeutics. SN - 0360-4012 UR - https://www.unboundmedicine.com/medline/citation/16385556/Antibodies_against_beta_amyloid_reduce_Abeta_oligomers_glycogen_synthase_kinase_3beta_activation_and_tau_phosphorylation_in_vivo_and_in_vitro_ L2 - https://doi.org/10.1002/jnr.20734 DB - PRIME DP - Unbound Medicine ER -