P3‐029: Alteration of protein kinase C in red blood cells: A potential marker for Alzheimer's disease

Abstract

dementing conditions. In recent years, several studies have found reduced levels of beta-amyloid protein and increased levels of total tau (T-tau) and phosphorylated tau (phosphotau) protein in the cerebrospinal fluid (CSF) of AD patients, suggesting a promising role of this method in the early diagnosis of disease. Similarly, the expression of tau protein was found to occur also in the oral mucosa epithelium of AD patients. Moreover, an increase of inflammatory mediators such as cytokines and chemokines has been identified in the CSF of these patients. This study investigated the levels of T-tau, phosphotau and beta amyloid proteins and of inflammatory mediators in the CSF and also in saliva of dementia patients, aiming to identify additional biomarkers for early AD diagnosis. Methods: We collected saliva and CSF from 75 individuals, namely 24 patients with probable AD, 18 patients with non-AD dementias and 33 cognitively healthy controls. Dosage of proteins in saliva and CSF was performed by ELISA. Phosphotau, T-tau, beta-amyloid protein, IL-08, MCP, IP10 are the markers that were evaluated in CSF and in saliva were measured T-tau, phosphotau and beta amyloid protein. Comparisons between concentrations of the different markers among the three diagnostic groups were undertaken by ANOVA and Kruskal-Wallis statistical tests. Results: The levels of phosphotau and T-tau proteins in the CSF were significantly increased in AD patients in comparison with healthy controls and non-AD patients. No significant difference in beta amyloid levels emerged between the three groups. Concerning the inflammatory mediators, a significant increase in MCP levels was observed in the non-AD group in comparison with AD and non-demented subjects. IL-08 as IP10 levels were not different between the three groups. No differences between the three groups were indentified with respect to the presence of all markers in saliva. Conclusions: The present study confirms the role of CSF T-tau and phosphotau levels as potential biomarkers in AD diagnosis, although not supporting the potential role of saliva as an alternative biological fluid for determination of these proteins.Background: Amyloid beta peptides are of particular interest in the study of Alzheimer's and other neurodegenerative diseases because these APP fragments are associated with plaques that form in the brains of afflicted patients, inhibiting healthy neuronal activity. The use of an antibody coupled array and mass spectrometry for detection of amyloid beta fragments facilitates identification and simultaneous monitoring of multiple fragments in complex biological samples such as CSF and brain lysates. Methods: Microliter volumes of CSF and brain lysates were diluted in PBST and incubated with a ProteinChip array precoupled with a monoclonal antibody (6E10) specific to the N-terminus of Amyloid beta. After sample binding, the array surface was washed to remove non-specifically bound proteins, and a MALDI matrix (CHCA) added. The captured peptides were then analyzed by mass spectro...