Proteomics analysis of plasma for potential biomarkers in the diagnosis of Alzheimer's disease

Abstract

The objective of this study was to search for biological markers associated with Alzheimer's disease (AD). Plasma specimens obtained from ten pathologically diagnosed AD patients and ten non-demented (ND) control subjects were analyzed by a combination of 2-DE and MS. This strategy allowed us to identify six plasma proteins (alpha-1-antitrypsin, vitamin D-binding protein, inter-alpha-trypsin inhibitor family heavy chain-related protein, apolipoprotein J precursor, cAMP-dependent protein kinase catalytic subunit alpha 1, and an orf) whose 2-DE spot densities were different between the AD and ND groups. Due to their involvements in AD amyloid plaque formation, the plasma concentrations of alpha-1-antitrypsin and apolipoprotein J were further validated using either ELISA or Western blot. The results revealed that the plasma levels of alpha-1-antitrypsin in AD were higher than those of controls, confirming the 2-DE findings. However, no difference in total apolipoprotein J concentration was observed between the AD and ND groups. Considering the difference in resolving power to differentially quantitate protein isoforms provided by 2-DE and Western blot, 2-DE analysis combined with MS protein identification offers distinctive advantages when a disease-related protein isoform-specific variance is investigated.

Activity-dependent neuroprotector homeobox protein: A candidate protein identified in serum as diagnostic biomarker for Alzheimer's disease

“…Previous studies indicate that several proteins may be potential biomarkers in the diagnosis of AD, such as amyloid precursor protein (APP), β-amyloid, tau, angiotensin I converting enzyme (ACE), AAT, complement factor-H, α-2-macroglobulin and Apo A-IV [21][22][23][24][25]. In our study, we also identified and confirmed some proteins as previously mentioned.…”

LeukocyteCCR2Expression Is Associated with Mini-Mental State Examination Score in Older Adults

“…31 The differences could arise from different patient selection criteria; we used population data rather than data from clinical settings. Differences with prior proteomic findings in peripheral blood in cognitive decline 32,33 may also be due to small study sizes or the possibility that circulating cytokines previously found associated with cognitive decline may be expressed by activated central nervous system (CNS) inflammatory cells and released into the circulation, rather than being expressed by circulating leukocytes. 34 The CCR2 receptor binds CCL2, a protein that is abundantly expressed in macrophage-rich areas of atherosclerotic plaques and in brain microglia, 7 resulting in migration of macrophages and brain microglial cells to their site of action.…”

Biobanks for biomarkers in neurological disorders

“…MS can detect subtle protein changes that cannot be detected using current techniques. Liao et al [6] performed a proteomic analysis of plasma for potential biomarkers by using a combination of 2-DE combined with MS.…”