Journal of Central Nervous System Disease

Alzheimer’s disease (AD) is the most common neurodegenerative disorder. Currently available therapies are symptomatic but do not alter underlying disease progression. Immunotherapeutic approaches such as anti Aß peptide active vaccination trials have had limited success to date. Intravenous immunoblobulin (IVIg) is widely used in immune-mediated neurological disorders such myasthenia gravis and Guillain-Barre syndrome. These preparations have been obtained from the pooled plasma of healthy human donors and contain natural anti-amyloid antibodies and are well tolerated. A small pilot study of passive immunotherapy using IVIg has suggested cognitive improvement. A multicenter phase III trial is ongoing and will determine whether or not this treatment can ameliorate cognitive deficits in mild-to-moderate AD. Here, we briefly review the pathogenic role of amyloid and tau in AD, as well as immunotherapeutic efforts to date. We also summarize what is known about naturally occurring anti-Aß and tau antibodies in IVIg with a view toward explaining potential mechanisms underlying their therapeutic effects.