Dementia Japan24:122-128, 2010

Clinical trials with Aβ immunotherapy for Alzheimer's Disease

Masahito Yamada

Department of Neurology and Neurobiology of Aging, Kanazawa University Graduate School of Medical Science

    This article reviews clinical trials of amyloid-β protein (Aβ) immunotherapy for Alzheimer's disease (AD).  The first human phase 1 clinical trial of immunization with Aβ1-42 (AN1792;Elan Pharmaceuticals) started in 2000 involving 80 patients with AD.  In a recent report of the long-term effects of this phase 1 trial, eight autopsied patients showed a reduction of Aβ plaques with increased blood anti-Aβ antibody levels, but no evidence of a delay of disease progression to severe dementia and death, suggesting that anti-amyloid therapies against AD may be too late at the stage of dementia.  The phase 2 clinical trial was stopped by occurrence of T-lymphocytic mengigoencephalitis in 6% of the immunized patients.  The power of the trials was insufficient to evaluate its clinical efficacy, and soluble Aβ oigomers, toxic Aβ species, were unknown in the brains from the immunized patients.  In the immunized patients, cerebral amyloid angiopathy (CAA) and CAA-related microhemorrhages increased, although Aβ might be cleared from cerebral vessels over prolonged time in some patients.  Currently, several clinical trials with passive or active Aβ immunotherapies are ongoing.  Future clinical trials of Aβ immunotherapies require regulation of meningoencephalitis and vascular complications related to CAA.


Address correspondence to Dr.Masahito Yamada, Department of Neurology and Neurobiology of Aging, Kanazawa University Graduate School of Medical Science(13-1 Takara-machi, Kanazawa, Ishikawa 920-8640, Japan)