Snellman, Anniina, Rokka, Johanna, Lopez-Picon, Francisco R, Helin, Semi, La Ferla, Barbara, Torittu, Annamari, Löyttyniemi, Eliisa, Pihlaja, Rea, Masserini, Massimo, Solin, Olof, Rinne, Juha O and Haaparanta-Solin, Merja (2017) Treatment effect of functionalized nanoliposomes to beta-amyloid deposition in APP23 transgenic mouse model of Alzheimer’s disease – A follow-up study using [11C]PIB micro-PET imaging. Neurobiology of aging, 57. pp. 84-94. ISSN 01974580

Abstract

Follow-up of β-amyloid (Aβ) deposition in vivo in transgenic mouse models of Alzheimer’s disease is a valuable translational tool in the preclinical evaluation of potential Aβ-centric therapies. Recently, functionalized nanoliposomes (mApoE-PA-LIPs) affecting Aβ aggregation and clearance have been developed. Our aim was to follow the effect of mApoE-PA-LIPs to cerebral Aβ deposition in APP23 mouse model of AD in vivo using longitudinal follow-up with [11C]PIB PET.
Transgenic APP23 mice were injected with mApoE-PA-LIP (n = 5) or saline (n = 7) three times per week intraperitoneally for 3 weeks. Mice were imaged with 60 min dynamic [11C]PIB PET scans at baseline before the treatment period (baseline at 16-17 mo), after the treatment (week 4; follow-up 1 at 17-18 mo) and after additional follow-up period of 3 mo (week 18; follow-up 2 at 20-21 mo) using Inveon multimodality PET/CT. PET data was quantitated as bound-to-free ratios at 40−60 min after injection (B/F40-60) and differences in frontal cortex (FC), neocortex (NC) and hippocampus (HC) were compared between groups. After follow-up 2, mice were sacrificed, brains dissected, and total Aβ plaque area, accompanying microgliosis and total brain soluble- and insoluble-Aβ1-40 was assessed with immunohistochemistry and ELISA, respectively.
At baseline, B/F40-60 for FC was 0.41 (0.14, n = 5) for mApoE-PA-LIP and 0.21 (0.27, n = 7) for saline injected mice. After the treatment, B/F40-60 for FC remained 0.41 (0.25, n = 5, -1%) in the mApoE-PA-LIP group, but increased to 0.46 (0.28, n = 5, + 106%) in the saline group; however, the difference between groups over time was not statistically significant due to high variation within groups (P = 0.21). After additional follow-up period, B/F40-60 for FC further increased in both groupsto 0.99 (0.21, n = 4) in mApoE-PA-LIP and 0.90 (0.33, n = 5) in saline group, and correlated well with total area of Aβ1-40 stained plaques (Pearson r = 0.88, P < 0.0001). Levels of total brain insoluble-Aβ1-40 and area of Aβ deposits were equivalent between groups in follow-up 2.

Item Type:	Article
Date Deposited:	27 Aug 2019 00:45
Last Modified:	27 Aug 2019 00:45
URI:	https://oak.novartis.com/id/eprint/31729