Human fibroblast and stem cell resource from the Dominantly Inherited Alzheimer Network.

BACKGROUND: Mutations in amyloid precursor protein (APP), presenilin 1 (PSEN1) and presenilin 2 (PSEN2) cause autosomal dominant forms of Alzheimer disease (ADAD). More than 280 pathogenic mutations have been reported in APP, PSEN1, and PSEN2. However, understanding of the basic biological mechanisms that drive the disease are limited. The Dominantly Inherited Alzheimer Network (DIAN) is an international observational study of APP, PSEN1, and PSEN2 mutation carriers with the goal of determining the sequence of changes in presymptomatic mutation carriers who are destined to develop Alzheimer disease. RESULTS: We generated a library of 98 dermal fibroblast lines from 42 ADAD families enrolled in DIAN. We have reprogrammed a subset of the DIAN fibroblast lines into patient-specific induced pluripotent stem cell (iPSC) lines. These cells were thoroughly characterized for pluripotency markers. CONCLUSIONS: This library represents a comprehensive resource that can be used for disease modeling and the development of novel therapeutics.

Sensitive ultrasonic detection of dystrophic skeletal muscle in patients with duchenne muscular dystrophy using an entropy-based signal receiver.

The dystrophinopathies comprise a group of X-linked genetic diseases that feature dystrophin deficiency. Duchenne and Becker muscular dystrophy are characterized by progressive weakness and wasting of skeletal, smooth, and/or cardiac muscle. Duchenne muscular dystrophy (DMD) is the most severe dystrophinopathy, with an incidence of 1:3500 male births. Despite understanding the structural and genetic basis for DMD, the pathogenesis and clinical basis for more severe involvement in specific skeletal muscle groups and the heart are poorly understood. Current techniques, such as strength testing for monitoring progress of disease and therapy in DMD patients, are imprecise and physically demanding for test subjects. Ultrasound is well-suited to detect changes in structure and organization in muscle tissue in a manner that makes low demands on the patient. Therefore, we investigated the use of ultrasound to quantitatively phenotype the remodeling process in patients with DMD. Beam-formed radio-frequency (RF) data were acquired from the skeletal muscles of nine DMD and five normal subjects imaged with a clinical imaging system (HDI5000 w/7 MHz probe applied above left biceps muscle). From these data, images were reconstructed using B-mode (log of analytic signal magnitude) and information-theoretic receivers (H(f)-receiver). H(f) images obtained from dystrophic muscle contained extensive "mottled" regions (i.e., areas with heterogeneous image contrast) that were not readily apparent from the B-Mode images. The 2-D autocorrelation of DMD H(f) images have broader peaks than those of normal subjects, which is indicative of larger scatterer sizes, consistent with pathologic changes of fibers, edema and fatty infiltration. Comparison of the relative peak widths (full width measured at 60% maximum) of the autocorrelation of the DMD and normal H(f) images shows a quantitative difference between the two groups (p < 0.005, student two-tailed paired t-test). Consequently, these imaging techniques may prove useful for longitudinal monitoring of disease progression and therapy.