title: Intranasal Administration of a Polyethylenimine-Conjugated Scavenger Peptide Reduces Amyloid-β Accumulation in a Mouse Model of Alzheimer's Disease.
abstract: Amyloid-β (Aβ) aggregation in the brain plays a central and initiatory role in pathogenesis and/or progression of Alzheimer's disease (AD). Inhibiting Aβ aggregation is a potential strategy in the prevention of AD. A scavenger peptide, V24P(10-40), designed to decrease Aβ accumulation in the brain, was conjugated to polyethylenimine (PEI) and tested as a preventive/therapeutic strategy for AD in this study. This PEI-conjugated V24P(10-40) peptide was delivered intranasally, as nasal drops, to four-month-old APP/PS1 double transgenic mice for four or eight months. Compared with control values, peptide treatment for four months significantly reduced the amount of GdnHCl-extracted Aβ40 and Aβ42 in the mice's hippocampus and cortex. After treatment for eight months, amyloid load, as quantified by Pittsburgh compound B microPET imaging, was significantly decreased in the mice's hippocampus, cortex, amygdala, and olfactory bulb. Our data suggest that this intranasally delivered scavenger peptide is effective in decreasing Aβ accumulation in the brain of AD transgenic mice. Nasal application of peptide drops is easy to use and could be further developed to prevent and treat AD.
authors.affiliation: Institute of Biological Chemistry, Academia Sinica, Taipei, Taiwan.|Institute of Biochemical Sciences, National Taiwan University, Taipei, Taiwan.
authors.forename: Chih-Yun
authors.initials: CY
authors.lastname: Lin
authors.affiliation: Institute of Biomedical Sciences, Academia Sinica, Taipei, Taiwan.
authors.forename: Yu-Sung
authors.initials: YS
authors.lastname: Cheng
authors.affiliation: Institute of Biological Chemistry, Academia Sinica, Taipei, Taiwan.
authors.forename: Tai-Yan
authors.initials: TY
authors.lastname: Liao
authors.affiliation: Institute of Biological Chemistry, Academia Sinica, Taipei, Taiwan.
authors.forename: Chen
authors.initials: C
authors.lastname: Lin
authors.affiliation: Institute of Biological Chemistry, Academia Sinica, Taipei, Taiwan.
authors.forename: Zih-Ten
authors.initials: ZT
authors.lastname: Chen
authors.affiliation: Institute of Biological Chemistry, Academia Sinica, Taipei, Taiwan.
authors.forename: Woan-Ing
authors.initials: WI
authors.lastname: Twu
authors.affiliation: Biomedical Imaging Research Center, Department of Nuclear Medicine, National Yang Ming University and Taipei Veterans General Hospital, Taipei, Taiwan.
authors.forename: Chi-Wei
authors.initials: CW
authors.lastname: Chang
authors.affiliation: Biomedical Imaging Research Center, Department of Nuclear Medicine, National Yang Ming University and Taipei Veterans General Hospital, Taipei, Taiwan.
authors.forename: David Tat-Wei
authors.initials: DT
authors.lastname: Tan
authors.affiliation: Biomedical Imaging Research Center, Department of Nuclear Medicine, National Yang Ming University and Taipei Veterans General Hospital, Taipei, Taiwan.|Molecular and Genetic Imaging Core, Taiwan Mouse Clinic, Academia Sinica, Taipei, Taiwan.
authors.forename: Ren-Shyan
authors.initials: RS
authors.lastname: Liu
authors.affiliation: Institute of Biomedical Sciences, Academia Sinica, Taipei, Taiwan.
authors.forename: Pang-Hsien
authors.initials: PH
authors.lastname: Tu
authors.affiliation: Institute of Biological Chemistry, Academia Sinica, Taipei, Taiwan.|Institute of Biochemical Sciences, National Taiwan University, Taipei, Taiwan.
authors.forename: Rita P-Y
authors.initials: RP
authors.lastname: Chen
mesh_terms: D000281:Administration, Intranasal; D000544:Alzheimer Disease / Q000000981:diagnostic imaging / Q000188:drug therapy* / Q000235:genetics; D016229:Amyloid beta-Peptides / Q000008:administration & dosage / Q000737:chemistry / Q000378:metabolism; D016564:Amyloid beta-Protein Precursor / Q000235:genetics; D000814:Aniline Compounds / Q000493:pharmacokinetics; D000818:Animals; D052160:Benzothiazoles / Q000493:pharmacokinetics; D045744:Cell Line, Tumor; D004195:Disease Models, Animal; D006801:Humans; D051379:Mice; D008822:Mice, Transgenic; D009154:Mutation / Q000235:genetics; D009447:Neuroblastoma / Q000473:pathology; D010446:Peptide Fragments / Q000008:administration & dosage / Q000737:chemistry / Q000378:metabolism; D011094:Polyethyleneimine / Q000008:administration & dosage*; D049268:Positron-Emission Tomography; D053764:Presenilin-1 / Q000235:genetics; D013844:Thiazoles / Q000493:pharmacokinetics
chemical_list: C475519:2-(4'-(methylamino)phenyl)-6-hydroxybenzothiazole; D016229:Amyloid beta-Peptides; D016564:Amyloid beta-Protein Precursor; D000814:Aniline Compounds; D052160:Benzothiazoles; D010446:Peptide Fragments; D053764:Presenilin-1; D013844:Thiazoles; C078592:amyloid beta-protein (1-40); C075222:amyloid beta-protein (1-42); D011094:Polyethyleneimine
keywords: Aggregate; Alzheimer’s disease; D-proline; amyloid; amyloid-β; fibril; peptide inhibitor; scavenger peptide; therapy