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-β (Aβ) aggregates to amyloid plaques in AD brains. As a result, many therapeutic approaches target Aβ. Human plasma and the plasma product intravenous immunoglobulin (IVIG) contain naturally-occurring anti-Aβ antibodies (Nabs-Aβ) that appear to reduce risks of developing AD. IVIG sequesters Aβ and thus interferes with AD progression. This study reviews the role of different Aβ species, Nabs-Aβ, 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-Aβ 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.