In Vivo Preclinical Assessment of β-Amyloid–Affine [11C]C-PIB Accumulation in Aluminium-Induced Alzheimer’s Disease-Resembling Hypercholesterinaemic Rat Model

Képes, Zita and Barkóczi, Alexandra and Szabó, Judit P. and Kálmán-Szabó, Ibolya and Arató, Viktória Zsófia and Jószai, István and Deák, Ádám and Kertész, István and Hajdu, István and Trencsényi, György (2022) In Vivo Preclinical Assessment of β-Amyloid–Affine [11C]C-PIB Accumulation in Aluminium-Induced Alzheimer’s Disease-Resembling Hypercholesterinaemic Rat Model. INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES, 23 (22). ISSN 1661-6596

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Abstract

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.

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