A blood-based biomarker panel indicates IL-10 and IL-12/23p40 are jointly associated as predictors of β-amyloid load in an AD cohort

Abstract

Alzheimer’s Disease (AD) is the most common form of dementia, characterised by extracellular amyloid deposition as plaques and intracellular neurofibrillary tangles of tau protein. As no current clinical test can diagnose individuals at risk of developing AD, the aim of this project is to evaluate a blood-based biomarker panel to identify individuals who carry this risk. We analysed the levels of 22 biomarkers in clinically classified healthy controls (HC), mild cognitive impairment (MCI) and Alzheimer’s participants from the well characterised Australian Imaging, Biomarker and Lifestyle (AIBL) study of aging. High levels of IL-10 and IL-12/23p40 were significantly associated with amyloid deposition in HC, suggesting that these two biomarkers might be used to detect at risk individuals. Additionally, other biomarkers (Eotaxin-3, Leptin, PYY) exhibited altered levels in AD participants possessing the APOE ε4 allele. This suggests that the physiology of some potential biomarkers may be altered in AD due to the APOE ε4 allele, a major risk factor for AD. Taken together, these data highlight several potential biomarkers that can be used in a blood-based panel to allow earlier identification of individuals at risk of developing AD and/or early stage AD for which current therapies may be more beneficial.

Plasma Aβ42 as a Biomarker of Prodromal Alzheimer’s Disease Progression in Patients with Amnestic Mild Cognitive Impairment: Evidence from the PharmaCog/E-ADNI Study

“…However, the collected plasma and DNA samples may be suitable for other AD blood biomarker candidates of interest, including a variety of protein, lipid, and microRNA species, as well as mitochondrial genes or DNA epigenetic modification patterns [25][26][27][28][29][30][31][32]. They may be evaluated in future studies carried out in PharmaCog/E-ADNI "positive" and "negative" aMCI groups.…”

Update on Biomarkers For Amyloid Pathology in Alzheimer’s Disease

“…In the advent of large well characterized research cohorts that now include Aβ PET and/or CSF Aβ measures as routine, the opportunity to use an "endophenotype" approach to discover peripheral markers of Aβ pathology is ever increasing. Pilot data suggest associations of the concentrations of a number of plasma proteins (e.g., pancreatic polypeptide Y, IgM, chemokine ligand 13, interleukin 17, vascular cell adhesion protein 1, 2-macroglobulin, apolipoprotein A1, fibrinogen gamma chain, interleukins and complement proteins) and metabolites with Aβ burden in the brain [128][129][130][131][132][133][134]. However, these data should be interpreted with some caution, as they are derived from multi-marker panels and as a mechanistic understanding of the associations is currently lacking.…”

Blood‐based protein predictors of dementia severity as measured by δ: Replication across biofluids and cohorts

“…IL‐12 is a similarly important PRO‐inflammatory protein, and antagonizes many of IL‐10's effects. Both are associated with amyloid deposition in the Australian Imaging, Biomarker & Lifestyle Flagship Study on Ageing (ABIL) [43]. IL‐12 is also unavailable in the ADNI, but loads significantly on INFLAMMATION in the TARCC, and inversely to IL‐10 (data not shown).…”