Investigation of relationships between Aß1-40, Aß1-42, sRAGE, esRAGE, sLRP1, Aß oligomer and neprilysin in patients with alzheimer's disease

Beta-amyloid (Aß), the key component of the amyloid plaque, has been shown to be central to Alzheimer?s disease (AD) pathogenesis. According to a widely accepted view, Aß oligomers are responsible for the formation of the disease. The cause of Aß deposition in sporadic type AD which accounts for more than %99 of all disease cases, however, remains unclear. Over production of Aß is observed in the familial type AD, but there is no evidence if this situation is also observed in the sporadic type AD. Deficiencies in the Aß clearance or enzyme-mediated Aß degradation are thought to be responsible for Aß accumulation in sporadic type AD. The aim of the study is to determine the plasma levels of Aß1-40, Aß1-42 and Aß oligomers and the serum levels of neprilysin which is main proteolytic enzyme of the Aß in the brain and sLRP which is secreted form the transporter of Aß from brain to blood, also known as LRP. We also determined the serum levels of sRAGE and esRAGE which are the secreted forms of RAGE, the carrier of Aß from blood to brain.A total of 100 participants, composed of 50 patients with AD and 50 healthy controls were enrolled in the study. AD patients were divided in to three subgroups according to clinical stages: mild stage (CDR:1), moderate stage (CDR:2) and severe stage (CDR:3). Circulating levels of Aß1-40, Aß1-42, Aß oligomer, sRAGE, esRAGE, sLRP and neprilysin were determined by the ELISA method. Simultaneously, routine biochemical (liver enzymes, lipid profile, kidney function tests) and hematologic (erythrocytes, leukocytes, platelets, hemoglobin, hematocrit) parameters were measured by the autoanalyzer. Correlations of results with different variables (age, gender, mini mental stage examination, routin biochemical and hematological parameters) were also evaluated.No significant difference was found for circulating levels of Aß1-40, Aß1-42, Aß oligomer, sRAGE, esRAGE, sLRP ve neprilysin, between AD and control groups. Aß oligomer levels in patients after staging a severe stage were significantly lower than mild stage and control. Aß oligomers have 69% sensitivity and 84% specificity for detection of patients with severe stage. Serum sRAGE was significantly decreased in the severe stage when compared with the moderate stage. Also, serum esRAGE was significantly lower in the severe stage than the mild stage. Serum esRAGE was significantly higher in the AD patients treated with galantamin than patients treated with donepezil and rivastigmine. A correlation was found between the Aß1-42 and sRAGE in AD and control groups. In both groups, sRAGE correlated with esRAGE and the esRAGE/sRAGE ratio was determined as 1:3. A correlation was found between the age and Aß1-42 in AD patients. Additionally, in AD patients, MMSE correlated with Aß oligomer, sRAGE and esRAGE. Furthermore Aß1-42, sRAGE and sLRP correlated with kidney function tests in AD patients and a correlation was found Aß1-40 and erythrocyte counts.In conclusion, we think that the blood levels of Aß1-40, Aß1-42, sRAGE, esRAGE, sLRP and neprilysin could not be used as a diagnostic marker in AD patients. However, plasma Aß oligomers could be used for this purpose in patients in the severe stage. We report, for the first time, serum levels of esRAGE and neprilysin in AD patients. In addition there is only one report, besides our study, for the measure mean of blood levels Aß oligomers and sLRP in AD patients. For these reasons, additional studies are greatly needed to determine whether these parameters possess the capacito to aid in the clinical diagnosis of AD.