ment of Alzheimer disease (AD) are hampered by the lack of noninvasive biomarkers of the underlying pathology. Between 10% and 20% of patients clinically diagnosed with AD lack AD pathology at autopsy, 1-3 and community physicians may not diagnose AD in 33% of patients with mild signs and symptoms. 4 Thus, a diagnostic biomarker may help clinicians separate patients who have AD pathology from those who do not. See also pp 261 and 304.

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In this work, we propose a diffusion MRI protocol for mining Parkinson's disease diffusion MRI datasets and recover robust disease-specific biomarkers. Using advanced high angular resolution diffusion imaging (HARDI) crossing fiber modeling and tractography robust to partial volume effects, we automatically dissected 50 white matter (WM) fascicles. These fascicles connect deep nuclei (thalamus, putamen, pallidum) to different cortical functional areas (associative, motor, sensorimotor, limbic), basal forebrain and substantia nigra. Then, among these 50 candidate WM fascicles, only the ones that passed a test-retest reproducibility procedure qualified for further tractometry analysis. Leveraging the unique 2-timepoints test-retest Parkinson's Progression Markers Initiative (PPMI) dataset of over 600 subjects, we found statistically significant differences in tract profiles along the subcortico-cortical pathways between Parkinson's disease patients and healthy controls. In particular, significant increases in FA, apparent fiber density, tract-density and generalized FA were detected in some locations of the nigro-subthalamo-putaminal-thalamo-cortical pathway. This connection is one of the major motor circuits balancing the coordination of motor output. Detailed and quantifiable knowledge on WM fascicles in these areas is thus essential to improve the quality and outcome of Deep Brain Stimulation, and to target new WM locations for investigation.

Our results demonstrate that miR-155 regulates proinflammatory responses in both blood-derived and central nervous system (CNS)-resident myeloid cells, in addition to impacting subsequent adaptive immune responses. Differential miRNA expression may therefore provide insight into mechanisms responsible for distinct phenotypic and functional properties of myeloid cells, thus impacting their ability to influence CNS injury and repair.

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Remyelination of lesions in the central nervous system contributes to neural repair following clinical relapses in multiple sclerosis. Remyelination is initiated by recruitment and differentiation of oligodendrocyte progenitor cells (OPCs) into myelinating oligodendrocytes. Simvastatin, a blood-brain barrierpermeable statin in multiple sclerosis clinical trials, has been shown to impact the in vitro processes that have been implicated in remyelination. Animals were fed a cuprizone-supplemented diet for 6 weeks to induce localized demyelination in the corpus callosum; subsequent return to normal diet for 3 weeks stimulated remyelination. Simvastatin was injected intraperitoneally during the period of coincident demyelination and OPC maturation (weeks 4 to 6), throughout the entire period of OPC responses (weeks 4 to 9), or during the remyelination-only phase (weeks 7 to 9). Simvastatin treatment (weeks 4 to 6) caused a decrease in myelin load and both Olig2 strong and Nkx2.2 strong OPC numbers. Simvastatin treatment (weeks 4 to 9 and 7 to 9) caused a decrease in myelin load, which was correlated with a reduction in Nkx2.2 strong OPCs and an increase in Olig2 strong cells, suggesting that OPCs were maintained in an immature state (Olig2 strong /Nkx2.2 weak ). NogoA؉ oligodendrocyte numbers were decreased during all simvastatin treatment regimens. Our findings suggest that simvastatin inhibits central nervous system remyelination by blocking progenitor differentiation , indicating the need to monitor effects of systemic immunotherapies that can access the central nervous system on brain tissuerepair processes.

Background Florbetapir F 18 (18F-AV-45) is a positron emission tomography (PET) imaging ligand for the detection of amyloid aggregation associated with Alzheimer’s disease. Earlier data showed that florbetapir F 18 binds with high affinity to β-amyloid plaques in human brain homogenates (Kd = 3.7 nM) and has favorable imaging pharmacokinetic properties, including rapid brain penetration and washout. The present study used human autopsy brain tissue to evaluate the correlation between in vitro florbetapir F 18 binding and β-amyloid density measured by established neuropathological methods. Methods The localization and density of florbetapir F 18 binding in frozen and formalin-fixed paraffin-embedded sections of postmortem brain tissue from 40 subjects with a varying degree of neurodegenerative pathology was assessed by standard florbetapir F 18 autoradiography and correlated with the localization and density of β-amyloid identified by silver staining, thioflavin S staining, and immunohistochemistry. Results There were strong quantitative correlations between florbetapir F 18 tissue binding and both β-amyloid plaques identified by light microscopy (sliver staining and thioflavin S fluorescence) and by immunohistochemical measurements of β-amyloid using three antibodies recognizing different epitopes of the β-amyloid peptide (Aβ). Florbetapir F 18 did not bind to neurofibrillary tangles. Conclusion Florbetapir F 18 selectively binds β-amyloid in human brain tissue. The binding intensity was quantitatively correlated with the density of β-amyloid plaques identified by standard neuropathological techniques and correlated with the density of Aβ measured by immunohistochemistry. Since β-amyloid plaques are a defining neuropathological feature for Alzheimer’s disease, these results support the use of florbetapir F 18 as an amyloid PET ligand to identify the presence of AD pathology in patients with signs and symptoms of progressive late-life cognitive impairment.