In Vivo Preclinical Assessment of β-Amyloid–Affine [11C]C-PIB Accumulation in Aluminium-Induced Alzheimer’s Disease-Resembling Hypercholesterinaemic Rat Model
Autor: | Zita Képes, Alexandra Barkóczi, Judit P. Szabó, Ibolya Kálmán-Szabó, Viktória Arató, István Jószai, Ádám Deák, István Kertész, István Hajdu, György Trencsényi |
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Jazyk: | angličtina |
Rok vydání: | 2022 |
Předmět: | |
Zdroj: | International Journal of Molecular Sciences, Vol 23, Iss 22, p 13950 (2022) |
Druh dokumentu: | article |
ISSN: | 1422-0067 1661-6596 |
DOI: | 10.3390/ijms232213950 |
Popis: | Aluminum (Al) excess and hypercholesterinaemia are established risks of Alzheimer’s disease (AD). The aim of this study was to establish an AD-resembling hypercholesterinaemic animal model—with the involvement of 8 week and 48 week-old Fischer-344 rats—by Al administration for the safe and rapid verification of β-amyloid-targeted positron emission tomography (PET) radiopharmaceuticals. Measurement of lipid parameters and β-amyloid–affine [11C]C-Pittsburgh Compound B ([11C]C-PIB) PET examinations were performed. Compared with the control, the significantly elevated cholesterol and LDL levels of the rats receiving the cholesterol-rich diet support the development of hypercholesterinaemia (p ≤ 0.01). In the older cohort, a notably increased age-related radiopharmaceutical accumulation was registered compared to in the young (p ≤ 0.05; p ≤ 0.01). A monotherapy-induced slight elevation of mean standardised uptake values (SUVmean) was statistically not significant; however, adult rats administered a combined diet expressed remarkable SUVmean increment compared to the adult control (SUVmean: from 0.78 ± 0.16 to 1.99 ± 0.28). One and two months after restoration to normal diet, the cerebral [11C]C-PIB accumulation of AD-mimicking animals decreased by half and a third, respectively, to the baseline value. The proposed in vivo Al-induced AD-resembling animal system seems to be adequate for the understanding of AD neuropathology and future drug testing and radiopharmaceutical development. |
Databáze: | Directory of Open Access Journals |
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