Investigating blood plasma levels of cytokines and amyloid-β as potential diagnostic biomarkers for preclinical Alzheimer’s disease
thesisposted on 2022-03-28, 10:52 authored by Mitra Elmi
Alzheimer’s disease (AD) is the most common form of dementia, but to date there is no effective treatment. Therefore, preclinical diagnosis is necessary to prevent or improve therapeutic approaches for disease management. Mounting evidence shows that inflammatory processes involving various pro-inflammatory cytokines including interleukin (IL)-1β, IL-6 and tumour necrosis factor (TNF)-α contribute to AD pathogenesis. While inflammatory biomarkers have been extensively studied in clinically diagnosed AD subjects, there has been a paucity of information on inflammatory biomarkers in cognitively normal elderly subjects with a high neocortical amyloid-β load (NAL). Based on the findings of increased pro-inflammatory cytokines in clinical AD, I hypothesised that plasma levels of these cytokines are also increased in preclinical AD, and these increased cytokine levels may have diagnostic value, and functionally play a role in impairing cognition. In this study, approximately 100 plasma samples from healthy elderly adults with either high or low NAL were assessed for pro-inflammatory cytokines using conventional enzyme-linked immunosorbent assay (ELISA) kits. Furthermore, since plasma beta amyloid (Aβ) levels have recently been demonstrated to be altered in clinical AD, I investigated the levels of this peptide in preclinical AD. The Aβ results, which were expressed as the ratio of amyloid beta (Aβ) 40/42 were compared between low and high NAL subjects. The data collected were analysed using the statistical package for social sciences (SPSS). No significant differences in the plasma levels of all the pro-inflammatory cytokines were observed between the two groups, although there was a consistent trend of increased levels in the high NAL group. However, the ratio of Aβ 40/42 was significantly higher in the high NAL group compared to the low NAL, and receiver operating characteristic (ROC) curves were created to evaluate predictive models. The accuracy of prediction was increased when Aβ 40/42 was added to the base model. In conclusion, while the pro-inflammatory cytokines do not show promise as preclinical AD biomarkers based on the conventional ELISA assays used, the ratio of Aβ 40/42 is a potential candidate that merits inclusion in a diagnostic panel of biomarkers for preclinical diagnosis of AD.