Investigating plasma protein biomarkers in preclinical Alzheimer’s disease utilising an autosomal dominant Alzheimer’s disease cohort

Background: Previous plasma protein profiling studies revealed several candidate plasma protein biomarkers for diagnosing Alzheimer’s disease (AD). However, the association of these proteins with AD progression remains to be uncovered. Further, since blood-based biomarkers are easily accessible and cost-effective, these proteins could be the first-line diagnostics for preclinical AD.

Methods: A total of 110 participants of an autosomal dominant AD cohort, 31 mutation non-carriers (NC), 36 asymptomatic mutation carriers (aMC) and 43 symptomatic mutation carriers (sMC), were used in this study. Selected plasma proteins associated with metabolism, neuroprotection, inflammation, and immune response pathways, were measured using Luminex xMAP immunoassay and were compared between the study groups. Further, associations of these proteins with cognitive performance, imaging and CSF biomarkers of AD were investigated.

Results: A significant between-group difference was observed for plasma IGFBP-1 (p<0.05), wherein significantly higher plasma IGFBP-1 levels were observed in sMC compared with aMC and NC. In aMC, IGFBP-1 was positively associated with cortical glucose metabolism (p<0.05), and in sMC, significant positive correlations were found with language (p<0.01) and global cognition (p<0.05). Further, in sMC, IGFBP-6 was inversely associated with hippocampal volume (p<0.05) and CCL-11 was positively associated with language (p<0.05) and inversely associated with CSF p-tau (p<0.05).

Conclusion: The current study demonstrates plasma IGFBP-1 elevation in the symptomatic stage of autosomal dominant AD. Additionally, this thesis provides insight into the pattern of association of the investigated proteins relating to metabolism, neuroprotection, inflammation and immune response pathways with cognition and the established markers of the ADAD continuum. However, further research in a large, independent AD cohort using longitudinal study design and ultrasensitive measurement platform is required to validate the current findings.