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P2‐057: REMOVAL OF Aβ OLIGOMERS FROM THE BLOOD USING HOLLOW FIBERS: A POTENTIAL THERAPEUTIC SYSTEM FOR ALZHEIMER'S DISEASE
Author(s) -
Saito Yuta,
Kobayakawa Moe,
Sakata Miwa,
Kawaguchi Kazunori,
Morikawa Hiroshi Kawachi,
Ohashi Norimi,
Hiki Yoshiyuki,
Kato Masao,
Hasegawa Midori,
Yuzawa Yukio,
Kitaguchi Nobuya
Publication year - 2018
Publication title -
alzheimer's and dementia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 6.713
H-Index - 118
eISSN - 1552-5279
pISSN - 1552-5260
DOI - 10.1016/j.jalz.2018.06.742
Subject(s) - membrane , chromatography , hemodialysis , chemistry , monomer , whole blood , medicine , surgery , biochemistry , polymer , organic chemistry
antibodies generated, we selected a molecule showing a KD value of 6 nM for isoAsp7-Ab and displaying w 500fold selectivity over non-modified Ab. Immunohistochemical staining of tissue from human post mortem brain showed exclusive labelling of amyloid plaques. This pattern was also observed in brain samples from transgenic mice, where we observed a characteristic increase of isoAsp detection beginning with onset of plaque deposition and increasing with age and amyloid pathology. Based on Ab extraction and ELISA quantification, we conclude that the isoAsp content is low in micewith onset of pathology (4%) and increases with ageing of 5xFAD mice. A 12weeks treatment of transgenic mice led to a reduction of isoAsp-modified and total Ab load, suggesting that selective opsonization of modified amyloid is eliciting phagocytosis of non-modified peptides. In a second trial, we observed an amelioration of a behavioral phenotype in elevated plus maze upon treatment with the antibody. Conclusions:In addition to previous studies applying antibodies directed against pGlu-modified Ab, we show here that also isoAsp-modified Ab represents a vital target for immunotherapy. The results support the general concept that targeting modified Ab peptides, which might be underrepresented compared to full-length Ab, are attractive anchor points for a more directed approach of immunotherapy in order to reduce common side effects.