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

• Published in: International journal of molecular sciences Vol. 23; no. 22; p. 13950
• Main Authors: Képes, Zita, Barkóczi, Alexandra, Szabó, Judit P, Kálmán-Szabó, Ibolya, Arató, Viktória, Jószai, István, Deák, Ádám, Kertész, István, Hajdu, István, Trencsényi, György
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 12.11.2022; MDPI
• Subjects: [11C]C-Pittsburgh compound B ([11C]C PIB); Accumulation; Aluminum; aluminum (Al); Aluminum - toxicity; Alzheimer Disease - chemically induced; Alzheimer Disease - diagnostic imaging; Alzheimer Disease - pathology; Alzheimer's disease; Alzheimer’s disease (AD); Amyloid beta-Peptides; Animal cognition; Animal models; Animals; Biomarkers; Brain research; Cholesterol; Glucose; hypercholesterinaemia; In vivo methods and tests; Laboratories; Lipids; Low density lipoprotein; Metabolism; Neurodegeneration; Neuropathology; Pharmaceuticals; Positron emission; Positron emission tomography; positron emission tomography (PET); Positron-Emission Tomography - methods; Radiochemistry; Radioisotopes; Radiopharmaceuticals; Rats; Rodents; standardised uptake value (SUV); Statistical analysis; Tomography; β-Amyloid; hypercholesterinaemia; standardised uptake value (SUV); aluminum (Al); Alzheimer’s disease (AD); positron emission tomography (PET); [11C]C-Pittsburgh compound B ([11C]C PIB)
• ISSN: 1422-0067; 1661-6596; 1422-0067
• DOI: 10.3390/ijms232213950

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 [ C]C-Pittsburgh Compound B ([ C]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 ≤ 0.01 . In the older cohort, a notably increased age-related radiopharmaceutical accumulation was registered compared to in the young ( ≤ 0.05; ≤ 0.01 . A monotherapy-induced slight elevation of mean standardised uptake values (SUV ) was statistically not significant; however, adult rats administered a combined diet expressed remarkable SUV increment compared to the adult control (SUV : from 0.78 ± 0.16 to 1.99 ± 0.28). One and two months after restoration to normal diet, the cerebral [ C]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.