Longitudinal Neuroimaging Analysis in Mild-Moderate Alzheimer's Disease Patients Treated with Plasma Exchange with 5% Human Albumin

Altres ajuts: This study was funded by Grifols. [...] James T. Becker (Department of Psychiatry, Neurology and Psychology. University of Pittsburgh, Pittsburgh PA, USA) read and commented on an earlier draft of the manuscript. Jordi Bozzo PhD, CMPP (Grifols) is acknowledged for medical writing and editorial assistance in the preparation of the manuscript.Recently, modifications of Aβ levels in CSF and plasma associated with improvement in memory and language functions have been observed in patients with mild-moderate Alzheimer's disease (AD) treated with plasma exchange (PE) with albumin replacement. To detect structural and functional brain changes in PE-treated AD patients as part of a Phase II clinical trial. Patients received between 3 and 18 PE with albumin (Albutein ® 5%, Grifols) or sham-PE (controls) for 21 weeks (divided in one intensive and two maintenance periods) followed by 6-month follow-up. Brain perfusion assessed by SPECT scans using an automated software (NeuroGam ®) and brain structural changes assessed by MRI were performed at weeks 0 (baseline), 21, and 44 (with additional SPECT at weeks 9 and 33). Statistical parametric mapping (voxel-based analysis, SPM) and Z-scores calculations were applied to investigate changes to baseline. 42 patients were recruited (39 evaluable; 37 analyzed: 18 PE-treated; 19 controls). There was a trend toward decreasing hippocampi and total intracranial volume for both patient groups during the study (p < 0.05). After six months, PE-treated patients had less cerebral perfusion loss than controls in frontal, temporal, and parietal areas, and perfusion stabilization in Brodmann area BA38-R during the PE-treatment period (p < 0.05). SPM analysis showed stabilization or absence of progression of perfusion loss in PE-treated patients until week 21, not observed in controls. Mild-moderate AD patients showed decreased brain volume and impairment of brain perfusion as expected for the progression of the disease. PE-treatment with albumin replacement favored the stabilization of perfusion

Long-Term Decrease in VLA-4 Expression and Functional Impairment of Dendritic Cells during Natalizumab Therapy in Patients with Multiple Sclerosis

Myeloid and plasmacytoid dendritic cells (mDCs, pDCs) are central to the initiation and the regulation of immune processes in multiple sclerosis (MS). Natalizumab (NTZ) is a humanized monoclonal antibody approved for the treatment of MS that acts by blocking expression of VLA-4 integrins on the surface of leukocytes. We determined the proportions of circulating DC subsets and analyzed expression of VLA-4 expression in 6 relapsing-remitting MS patients treated with NTZ for 1 year. VLA-4 expression levels on pDCs and mDCs decreased significantly during follow-up. In vitro coculture of peripheral blood mononuclear cells and pDCs, with different doses of NTZ in healthy controls (HC) and MS patients showed dose-dependent down-regulation of VLA-4 expression levels in both MS patients and HC, and reduced functional ability to stimulate antigen-specific T-lymphocyte responses. The biological impact of NTZ may in part be attributable to inhibition of transmigration of circulating DCs into the central nervous system, but also to functional impairment of interactions between T cells and DC

Longitudinal Neuroimaging Analysis in Mild-Moderate Alzheimer's Disease Patients Treated with Plasma Exchange with 5% Human Albumin

Altres ajuts: This study was funded by Grifols. [...] James T. Becker (Department of Psychiatry, Neurology and Psychology. University of Pittsburgh, Pittsburgh PA, USA) read and commented on an earlier draft of the manuscript. Jordi Bozzo PhD, CMPP (Grifols) is acknowledged for medical writing and editorial assistance in the preparation of the manuscript.Recently, modifications of Aβ levels in CSF and plasma associated with improvement in memory and language functions have been observed in patients with mild-moderate Alzheimer's disease (AD) treated with plasma exchange (PE) with albumin replacement. To detect structural and functional brain changes in PE-treated AD patients as part of a Phase II clinical trial. Patients received between 3 and 18 PE with albumin (Albutein ® 5%, Grifols) or sham-PE (controls) for 21 weeks (divided in one intensive and two maintenance periods) followed by 6-month follow-up. Brain perfusion assessed by SPECT scans using an automated software (NeuroGam ®) and brain structural changes assessed by MRI were performed at weeks 0 (baseline), 21, and 44 (with additional SPECT at weeks 9 and 33). Statistical parametric mapping (voxel-based analysis, SPM) and Z-scores calculations were applied to investigate changes to baseline. 42 patients were recruited (39 evaluable; 37 analyzed: 18 PE-treated; 19 controls). There was a trend toward decreasing hippocampi and total intracranial volume for both patient groups during the study (p < 0.05). After six months, PE-treated patients had less cerebral perfusion loss than controls in frontal, temporal, and parietal areas, and perfusion stabilization in Brodmann area BA38-R during the PE-treatment period (p < 0.05). SPM analysis showed stabilization or absence of progression of perfusion loss in PE-treated patients until week 21, not observed in controls. Mild-moderate AD patients showed decreased brain volume and impairment of brain perfusion as expected for the progression of the disease. PE-treatment with albumin replacement favored the stabilization of perfusion