Plasma proteins predict conversion to dementia from prodromal disease

Abstract

BackgroundThe study aimed to validate previously discovered plasma biomarkers associated with AD, using a design based on imaging measures as surrogate for disease severity and assess their prognostic value in predicting conversion to dementia.MethodsThree multicenter cohorts of cognitively healthy elderly, mild cognitive impairment (MCI), and AD participants with standardized clinical assessments and structural neuroimaging measures were used. Twenty-six candidate proteins were quantified in 1148 subjects using multiplex (xMAP) assays.ResultsSixteen proteins correlated with disease severity and cognitive decline. Strongest associations were in the MCI group with a panel of 10 proteins predicting progression to AD (accuracy 87%, sensitivity 85%, and specificity 88%).ConclusionsWe have identified 10 plasma proteins strongly associated with disease severity and disease progression. Such markers may be useful for patient selection for clinical trials and assessment of patients with predisease subjective memory complaints.

Detection of the tau protein in human serum by a sensitive four-electrode electrochemical biosensor

“…Tau CSF levels have been measured with conventional methods such as enzyme-linked immunosorbent assay (ELISA), mass spectrometry or surface plasmon resonance, which are timeconsuming and/or expensive (Hye et al, 2014;Liu et al, 2014;Mehta et al, 2000;Sparks et al, 2012;Tuantranont, 2013). Researchers have made great efforts to generate rapid, cost-effective and highly sensitive detection tests using biosensors.…”

[O2–04–01]: Clearance of Beta‐amyloid Is Facilitated by Apolipoprotein E and Circulating High‐density Lipoproteins in Bioengineered Human Vessels

“…Specifically, levels of apoA-I, the major HDL-associated protein, positively correlate with Mini-Mental State Examination (MMSE) and Cognitive Ability Screening Instrument (CASI) scores (Merched et al, 2000) and high serum HDL-C levels (>55 mg/dl) in cognitively normal elderly individuals is associated with significantly reduced risk (HR 0.4) of AD even after adjusting for APOE genotype and vascular risk factors including obesity and T2DM (Reitz et al, 2010). In symptomatic AD patients, plasma apoA-I levels negatively correlate with hippocampal and whole brain volume as well as mean entorhinal cortical thickness (Hye et al, 2014), and decreased levels of serum apoA-I can discriminate AD from non-demented age-matched control subjects (Shih et al, 2014). As HDL and apoE have several potent vasoprotective functions including reducing inflammation, increasing vascular tone through promoting endothelial nitric oxide (NO) synthase activity, and suppressing vascular adhesion molecule expression (Stukas et al, 2014b;Sacre et al, 2003), an important goal is to understand how plasma-derived circulating (i.e.…”

Recent advances in biomarkers for Parkinson’s disease focusing on biochemicals, omics and neuroimaging

“…Due to heterogeneity in disease pathology and pathological overlap with other neurodegenerative disorders, it is likely that an optimal biomarker will combine multiple methodological approaches, i.e., a panel of markers will be needed for PD diagnosis/progression. For example, in their study of AD biomarkers, Abdul and colleagues have recently used a combination of 10 plasma proteins to predict conversion to dementia with an accuracy of 87%, sensitivity of 85%, and specificity of 88% [71]. Already, initiatives in PD are currently testing collaborative approaches for a combination of markers, possibly incorporating, in addition to imaging, clinical batteries, molecular genetics, and other disease state-based markers, as well as omics-based measures.…”