Intranasal Administration of a Polyethylenimine-Conjugated Scavenger Peptide Reduces Amyloid-β Accumulation in a Mouse Model of Alzheimer’s Disease

Article type: Research Article

Authors: Lin, Chih-Yun^{a; b} | Cheng, Yu-Sung^c | Liao, Tai-Yan^a | Lin, Chen^a | Chen, Zih-ten^a | Twu, Woan-Ing^a | Chang, Chi-Wei^d | Tan, David Tat-Wei^d | Liu, Ren-Shyan^{d; e} | Tu, Pang-hsien^{c; *} | Chen, Rita P.-Y.^{a; b; *}

Affiliations: [a] Institute of Biological Chemistry, Academia Sinica, Taipei, Taiwan | [b] Institute of Biochemical Sciences, National Taiwan University, Taipei, Taiwan | [c] Institute of Biomedical Sciences, Academia Sinica, Taipei, Taiwan | [d] Biomedical Imaging Research Center, Department of Nuclear Medicine, National Yang Ming University and Taipei Veterans General Hospital, Taipei, Taiwan | [e] Molecular and Genetic Imaging Core, Taiwan Mouse Clinic, Academia Sinica, Taipei, Taiwan

Correspondence: [*] Correspondence to: Rita P.-Y. Chen, Institute of Biological Chemistry, Academia Sinica, No. 128, Sec. 2, Academia Rd, Nankang, Taipei 11529, Taiwan. Tel.: +886 2 27855696; Fax: +886 2 27889759; E-mail: pyc@gate.sinica.edu.tw and Pang-hsien Tu, Institute of Biomedical Sciences, Academia Sinica, No. 128, Sec. 2, Academia Rd, Nankang, Taipei 11529, Taiwan; Tel.: +886 2 26523532; Fax: +886 2 27827654; E-mail: benrosetu@yahoo.com.

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.

Keywords: Aggregate, Alzheimer’s disease, amyloid, amyloid-β, D-proline, fibril, peptide inhibitor, scavenger peptide, therapy

DOI: 10.3233/JAD-151024

Journal: Journal of Alzheimer's Disease, vol. 53, no. 3, pp. 1053-1067, 2016