ADAM10 Plasma and CSF Levels Are Increased in Mild Alzheimer's Disease.

ADAM10 is the main α-secretase that participates in the non-amyloidogenic cleavage of amyloid precursor protein (APP) in neurons, inhibiting the production of ß-amyloid peptide (Aß) in Alzheimer's disease (AD). Strong recent evidence indicates the importance of the localization of ADAM10 for its activity as a protease. In this study, we investigated ADAM10 activity in plasma and CSF samples of patients with amnestic mild cognitive impairment (aMCI) and mild AD compared with cognitively healthy controls. Our results indicated that plasma levels of soluble ADAM10 were significantly increased in the mild AD group, and that in these samples the protease was inactive, as determined by activity assays. The same results were observed in CSF samples, indicating that the increased plasma ADAM10 levels reflect the levels found in the central nervous system. In SH-SY5Y neuroblastoma cells, ADAM10 achieves its major protease activity in the fraction obtained from plasma membrane lysis, where the mature form of the enzyme is detected, confirming the importance of ADAM10 localization for its activity. Taken together, our results demonstrate the potential of plasma ADAM10 to act as a biomarker for AD, highlighting its advantages as a less invasive, easier, faster, and lower-cost processing procedure, compared to existing biomarkers.

Impact of pulmonary regurgitation and age at surgical repair on textural and functional right ventricular myocardial properties in patients with tetralogy of Fallot.

BACKGROUND: The aim of this study was to identify non-invasively the potential impact of pulmonary regurgitation and age at surgical repair on the right ventricular (RV) textural and functional myocardial properties in patients operated on for tetralogy of Fallot (TOF). METHODS: We assessed the average intensity (Int.(1B)) and the cyclic variation (CV(IB)) of the echocardiographic backscatter curve in 30 TOF patients (mean age 16.2 +/- 8.3 years), who had undergone corrective surgery (mean age at repair 3.2 +/- 2.6 years, range 0.2-11 years). They were divided into three age- and body surface area (BSA)-matched subgroups according to the results of the surgical repair: 12 patients had no significant postsurgical sequelae (group I), 12 patients had isolated moderate-severe pulmonary regurgitation (group II), and 6 patients had pulmonary regurgitation associated with significant (> 30 mmHg) RV outflow tract obstruction (group III). In addition, 30 age-, sex- and BSA-matched normal subjects were identified as the control group. RESULTS: In our study population, CV(IB) was lower (7.86 +/- 2.5 vs 10.6 +/- 1.4 dB, p < 0.001) and Int.IB higher (-18.6 +/- 4.1 vs -21 +/- 2.8 dB, p = 0.01) compared to the control group. Comparison between the control group and each subgroup of TOF patients showed: a) comparable values of CV(IB) and Int.(IB) in group I (10.6 +/- 1.4 vs 9.4 +/- 2.3 dB, p = 0.07; and -21 +/- 2.8 vs -21.4 +/- 2.3 dB, p = 0.7, respectively); b) Int.(IB) was significantly different only in group III (-21 +/- 2.8 vs -13.3 +/- 4.6 dB, p < 0.0001), c) CV(IB) was different either in group II or III (10.6 +/- 1.4 vs 7.42 +/- 2, p < 0.001; and 10.6 +/- 1.4 vs 5.56 +/- 1.8, p < 0.001, respectively). In addition, comparison of integrated backscatter indexes among the TOF subgroups revealed significant differences of CV(IB) between group I and II (9.4 +/- 2.4 vs 7.4 +/- 2, p = 0.03) and between group I and III (9.4 +/- 2.4 vs 5.56 +/- 1.8, p = 0.004), and of Int.(IB) between group I and III (-21.4 +/- 2.3 vs -13.3 +/- 4.66, p < 0.001) and between group II and III (-21.4 +/- 2.3 vs -18.6 +/- 2.8, p = 0.006). Group III patients, who had the most significant RV dilation, expressed as the ratio between RV and left ventricular end-diastolic diameter (0.55 +/- 0.8) compared to group II (0.67 +/- 0.11, p = 0.038) and group I (0.55 +/- 0.87, p < 0.001), showed the lowest values of CV(IB) (5.56 +/- 1.8 dB) and the highest values of Int.(IB) (-13.3 +/- 4.6 dB) Finally, in our study population, both the degree of RV dilation and the age at surgical repair significantly correlated with Int.(IB) (r = 0.49 and r = 0.4, p = 0.06 and p = 0.033, respectively) and inversely correlated with CV(IB) (r = -0.55 and r = -0.53, p = 0.002 and p = 0.003, respectively). CONCLUSIONS: In patients operated on for TOF: a) integrated backscatter analysis may identify patients with significant RV myocardial abnormalities related to postsurgical sequelae; b) residual pulmonary regurgitation, particularly if associated with pulmonary stenosis, appears to affect RV myocardial properties; c) an earlier repair of TOF may result in better preservation of myocardial characteristics.