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Current Opinion in Psychiatry:
doi: 10.1097/YCO.0000000000000041
NEURODEVELOPMENTAL AND NEUROCOGNITIVE DISORDERS: Edited by James C. Harris and Perminder Sachdev

Is there still any hope for amyloid-based immunotherapy for Alzheimer's disease?

Panza, Francescoa,b; Logroscino, Giancarloa,b; Imbimbo, Bruno P.c; Solfrizzi, Vincenzod

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Abstract

Purpose of review: We reviewed clinical trials on active and passive anti-β-amyloid (Aβ) immunotherapy for the treatment of Alzheimer's disease with a particular focus on monoclonal antibodies against Aβ.

Recent findings: Studies on anti-Alzheimer's disease immunotherapy published in the period from January 2012 to October 2013 were reviewed.

Summary: Both active and passive anti-Aβ immunotherapies were shown to clear brain Aβ deposits. However, an active anti-Aβ vaccine (AN1792) has been discontinued because it caused meningoencephalitis in 6% of Alzheimer's disease patients treated. Among passive immunotherapeutics, two Phase III clinical trials in mild-to-moderate Alzheimer's disease patients with bapineuzumab, a humanized monoclonal antibody directed at the N-terminal sequence of Aβ, were disappointing. Another antibody, solanezumab, directed at the mid-region of Aβ, failed in two Phase III clinical trials in mild-to-moderate Alzheimer's disease patients. A third Phase III study with solanezumab is ongoing in mildly affected Alzheimer's disease patients based on encouraging results in this subgroup of patients. Second-generation active Aβ vaccines (ACC-001, CAD106, and Affitope AD02) and new passive anti-Aβ immunotherapies (gantenerumab and crenezumab) are being tested in prodromal Alzheimer's disease patients, in presymptomatic individuals with Alzheimer's disease-related mutations, or in asymptomatic individuals at risk of developing Alzheimer's disease to definitely test the Aβ cascade hypothesis of Alzheimer's disease.

© 2014 Wolters Kluwer Health | Lippincott Williams & Wilkins

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