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.