Serum Fragments of Tau for the Differential Diagnosis of Alzheimer's Disease.

Differential diagnosis of AD is still a challenge due to overlapping features with other types of dementia. Biomarkers for the differential diagnosis of AD can improve the diagnostic value of the disease and ensure an appropriate treatment of patients. The aim of this study was to evaluate the potential of two neo-epitope fragments of Tau as serum biomarkers for differential diagnosis of AD. The neo-epitope fragments of Tau were assessed in a cross-sectional cohort of subjects with AD, MCI, other dementias or subjects with non-dementia related memory complaints. The two Tau neo-epitope fragments were an ADAM10-generated fragment (Tau-A) and a caspase-3-generated fragment (Tau-C). The serum levels of the fragments were measured by two competitive ELISAs detecting Tau-A and Tau-C, respectively. Tau-A and Tau-C were able to separate subjects with AD and MCI from those with other dementias (p<0.0042 and p<0.05), and Tau-A could also discriminate between AD and MCI patients and subjects with non-dementia related memory complaints (p<0.05). Tau-A showed a significantly greater discrimination between AD and MCI subjects and patients with other dementias when compared to CSF biomarkers t-Tau and p-Tau. The ability of Tau-A to differentiate between AD and MCI from other dementias was comparable with CSF Aß1-42, t-Tau/Aß1-42 and p-Tau/Aß1-42. The separation between the diagnostic groups was significantly improved when the CSF biomarkers as well as age and BMI were used in combination with Tau-A (AUC=0.87, 95% CI: 0.75-0.94) (p<0.0001). In conclusion, this study shows that a neoepitope fragment of Tau detected in serum can provide guidance on the differential diagnosis of AD.

Uptake and transport of superparamagnetic iron oxide nanoparticles through human brain capillary endothelial cells.

The blood-brain barrier (BBB) formed by brain capillary endothelial cells (BCECs) constitutes a firm physical, chemical, and immunological barrier, making the brain accessible to only a few percent of potential drugs intended for treatment inside the central nervous system. With the purpose of overcoming the restraints of the BBB by allowing the transport of drugs, siRNA, or DNA into the brain, a novel approach is to use superparamagnetic iron oxide nanoparticles (SPIONs) as drug carriers. The aim of this study was to investigate the ability of fluorescent SPIONs to pass through human brain microvascular endothelial cells facilitated by an external magnet. The ability of SPIONs to penetrate the barrier was shown to be significantly stronger in the presence of an external magnetic force in an in vitro BBB model. Hence, particles added to the luminal side of the in vitro BBB model were found in astrocytes cocultured at a remote distance on the abluminal side, indicating that particles were transported through the barrier and taken up by astrocytes. Addition of the SPIONs to the culture medium did not negatively affect the viability of the endothelial cells. The magnetic force-mediated dragging of SPIONs through BCECs may denote a novel mechanism for the delivery of drugs to the brain.