Peripheral Delivery of a CNS Targeted, Metalo-Protease Reduces Aβ Toxicity in a Mouse Model of Alzheimer's Disease

Alzheimer's disease (AD), an incurable, progressive neurodegenerative disorder, is the most common form of dementia. Therapeutic options have been elusive due to the inability to deliver proteins across the blood-brain barrier (BBB). In order to improve the therapeutic potential for AD, we utilized a promising new approach for delivery of proteins across the BBB. We generated a lentivirus vector expressing the amyloid β-degrading enzyme, neprilysin, fused to the ApoB transport domain and delivered this by intra-peritoneal injection to amyloid protein precursor (APP) transgenic model of AD. Treated mice had reduced levels of Aβ, reduced plaques and increased synaptic density in the CNS. Furthermore, mice treated with the neprilysin targeting the CNS had a reversal of memory deficits. Thus, the addition of the ApoB transport domain to the secreted neprilysin generated a non-invasive therapeutic approach that may be a potential treatment in patients with AD

Integrating anatomical priors in ECT reconstruction via joint mixtures and mutual information

We present a joint mixture model for integrating anatomical information in ECT reconstruction. The mixture model acts as a Bayesian prior with the added benefit of the anatomical segmentation pixel-region labels guiding the reconstruction process. An additional hyper-prior on the mixture occupation probability is introduced. This has the novel interpretation of maximizing the mutual information between the anatomical image and the evolving ECT reconstruction. Results are presented on a phantom with the bias/variance tradeoff being the indicator of performance

Quantitative Effects of Using Thin-Plate Priors in Bayesian SPECT Reconstruction

Maximum a posteriori approaches in the context of a Bayesian framework have played an important role in SPECT reconstruction. The major advantages of these approaches include not only the capability of modeling the character of the data in a natural way but also the allowance of the incorporation of a priori information. Here, we show that a simple modification of the conventional smoothing prior, such as the membrane prior, to one less sensitive to variations in first spatial derivatives - the thin plate (TP) prior - yields improved reconstructions in the sense of low bias at little change in variance. Although the nonquadratic priors, such as the weak membrane and the weak plate, can exhibit good performance, they suffer difficulties in optimization and hyperparameter estimation. On the other hand, the thin plate, which is a quadratic prior, leads to easier optimization and hyperparameter estimation. In this work, we evaluate and compare quantitative performance of MM, TP, and FBP (f..