Affiliations: [a] Department of Vascular Dementia Research, National Institute for Longevity Sciences, National Center for Geriatrics and Gerontology, 36-3 Genko, Morioka, Obu, Aichi 474-8511, Japan | [b] Department of Neurology, 1st Affiliated Hospital, China Medical University, 155 North Nanjing Street, Shenyang 110001, P.R. China | [c] Department of Clinical Research, NHO Saigata National Hospital, 468-1 Saigata, Oogata, Jouetsu, Niigata 949-3193, Japan
Correspondence:
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Corresponding author: Takeshi Tabira, National Institute for Longevity Sciences, National Center for Geriatrics and Gerontology, 36-3 Genko, Morioka, Obu, Aichi 474-8511, Japan. Tel.: +81 562 45 0183; Fax: +81 562 45 0184; E-mail: tabira@nils.go.jp.
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Communicated by Akihiko Takashima.
Abstract: Tissue amyloid plaque immuno-reactive (TAPIR) antibody was better related to the effect of immunotherapy in Alzheimer's disease (AD) than ELISA antibody. Here we used a hybridoma technique to develop a TAPIR-like anti-human amyloid-β (Aβ) mouse monoclonal antibody. The obtained monoclonal antibody, 3.4A10, was an IgG2b isotype and recognized N-terminal portion of Aβ1–42 without binding denatured or native amyloid-β protein precursor. It had higher affinity to Aβ1–42 than to Aβ1–40 by Biacore affinity analysis and stained preferably the peripheral part of senile plaques and recognized the plaque core less than 4G8. It inhibited the Aβ1–42 fibril formation as well as degraded pre-aggregated Aβ1–42 peptide in a thioflavin T fluorescence spectrophotometry assay. The in vivo studies showed that 3.4A10 treatment decreased amyloid burden compared to the control group and significantly reduced Aβ42 levels rather than Aβ40 levels in brain lysates as well as the Aβ*56 oligomer (12mer) in TBS fraction of the brain lysates. 3.4A10 entered brain and decorated some plaques, which is surrounded by more Iba1-positive microglia. 3.4A10 therapy did not induce lymphocytic infiltration and obvious increase in microhemorrhage. We conclude that 3.4A10 is a TAPIR-like anti-human amyloid monoclonal antibody, and has a potential of therapeutic application for AD.
