Intravenous immunoglobulin for the treatment of Alzheimer's disease: current evidence and considerations.

Alzheimer's disease (AD) is a devastating neurodegenerative form of dementia with increasing incidence rates in most countries. AD is characterized by amyloid plaques and neurofibrillary tangles in the brains of AD individuals accompanied by global neuronal loss. The peptide amyloid-ß (Aß) aggregates to amyloid plaques in AD brains. As a result, many therapeutic approaches target Aß. Human plasma and the plasma product intravenous immunoglobulin (IVIG) contain naturally-occurring anti-Aß antibodies (Nabs-Aß) that appear to reduce risks of developing AD. IVIG sequesters Aß and thus interferes with AD progression. This study reviews the role of different Aß species, Nabs-Aß, preclinical data, and clinical studies of IVIG as potential AD treatments. The focus of this study is the outcomes of a recent Gammaglobulin Alzheimer's Partnership Phase III trial that did not reach primary endpoints, as well as efforts to compare IVIG with current anti-Aß monoclonals such as bapineuzumab, solanezumab, and BIIB037. Moreover, this study critically examines current market and ethical consequences of potential off-label uses of IVIG, limits in IVIG supply, and subsequent challenges.

Repetitive transcranial magnetic stimulation of the dorsolateral prefrontal cortex and cortical excitability in patients with major depressive disorder.

Repetitive transcranial magnetic stimulation (rTMS) of the dorsolateral prefrontal cortex is a relatively non-invasive technique with putative therapeutic effects in major depression. However, the exact neurophysiological basis of these effects needs further clarification. Therefore, we studied the impact of ten daily sessions of left, dorsolateral prefrontal rTMS on motor cortical excitability, as revealed by transcranial magnetic stimulation-elicited motor-evoked potentials in 30 patients. As compared to the non-responders, responders (33%) showed changes in parameters pointing towards a reduced cortical excitability. These results suggest that repetitive transcranial magnetic stimulation of the dorsolateral, prefrontal cortex may have inhibitory effects on motor cortical neuronal excitability in patients with major depressive disorder. Furthermore, measurement of motor cortical excitability may be a useful tool for investigating and monitoring inhibitory brain effects of antidepressant stimulation techniques like rTMS.