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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. [ABSTRACT FROM AUTHOR]

The neurotrophin receptor p75 (p75NTR) plays important roles in regulating amyloid-beta (Aβ) metabolism in the brain. The expression of p75NTR is altered in the brain of patients with Alzheimer's disease (AD). In this study, we aimed to evaluate whether p75NTR mRNA level in the peripheral blood cells is changed among AD patients and its potential to be a biomarker for AD. The study subjects included 26 patients with AD (PiB-PET positive) and 28 cognitively normal controls (PiB-PET negative). RNA was extracted from peripheral blood cells of fast blood. p75NTR mRNA was measured using quantitative real-time PCR assay. p75NTR mRNA levels in blood cells were comparable between AD patients and controls. p75NTR mRNA levels in blood cells were not correlated with MMSE scores, ApoE genotypes, gender, and age. p75NTR mRNA expression in blood cells is not changed in AD patients and is unlikely to be a biomarker for AD. [ABSTRACT FROM AUTHOR]

Pittsburgh compound B ([11C]PiB) was the first broadly applied radiotracer with specificity for amyloid-β (Aβ) peptide aggregates in the brain and has since been established as the gold standard for positron emission tomography (PET) employed for clinical in vivo imaging of Aβ plaques, used for imaging applications of Alzheimer's disease (AD), related dementia, and other tauopathies. The use of [11C]PiB for routine PET studies is dependent on the production capabilities of each radiochemistry laboratory, subsequently a continuous effort is made to develop suitable and sustainable methods on a variety of auto synthesis platforms. Here we report a fully automated, multi-step radio synthesis, purification, and reformulation of [11C]PiB for PET imaging using the Trasis AllinOne synthesis unit, a commonly used commercial radiochemistry module. We performed three validation runs to evaluate the reproducibility and to verify that the acceptable criteria were met for the release of clinical-grade [11C]PiB using a Trasis AllinOne auto radiosynthesis unit. Solid phase supported radiolabeling was performed through the capture of precursor (6-OH-BTA-0) on a C18 solid phase extraction (SPE) cartridge and subsequent flushing of gaseous [11C]Methyl triflate(MeOTf) through the Sep-Pak for carbon-11 (11C) N-methylation. Starting with 92.5 GBq [11C]CO 2 , [11C]PiB synthesis was completed in approximately 25 min after cyclotron end of bombardment with an injectable dose >7.0 GBq at end of the synthesis. The radiopharmaceutical product met all quality control criteria and specifications for use in human studies. • Automated radiosynthesis of [11C]PiB on the Trasis AllinOne synthesis unit. • Synthesis of the N-methylating synthon, [11C]MeOTf on the same cassette. • [11C]PiB was obtained with high molar activity and radiochemical purity. • Procedure is potentially transferable to the production of [11C]PiB in commercial kit modules. • [11C]PiB produced meets all quality control specifications for human use. [ABSTRACT FROM AUTHOR]