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- Title
In Vivo Preclinical Assessment of β-Amyloid–Affine [ 11 C]C-PIB Accumulation in Aluminium-Induced Alzheimer's Disease-Resembling Hypercholesterinaemic Rat Model.
- Authors
Képes, Zita; Barkóczi, Alexandra; Szabó, Judit P.; Kálmán-Szabó, Ibolya; Arató, Viktória; Jószai, István; Deák, Ádám; Kertész, István; Hajdu, István; Trencsényi, György
- 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.
- Subjects
PITTSBURGH (Pa.); ALZHEIMER'S disease; DISEASE risk factors; POSITRON emission tomography; RATS; ANIMAL disease models; LDL cholesterol
- Publication
International Journal of Molecular Sciences, 2022, Vol 23, Issue 22, p13950
- ISSN
1661-6596
- Publication type
Article
- DOI
10.3390/ijms232213950