Dementia Japan 23: 32-37, 2009

Amyloid beta vaccine therapy; peripheral sink hypothesis

Yasuji Matsuoka

Department of Neurology, Georgetown University Medical Center

    Senile plaques, neurofibrillary tangles and neuronal cell death are pathological hallmarks of Alzheimer's disease. Amyloid beta (Abeta) is a primary component of senile plaques, and generated from a parental molecule, amyloid precursor protein (APP). Therefore, enhancement of Abeta clearance is a promising therapeutic approach. Abeta immunotherapy reduces brain Abeta load, and two mechanisms were proposed: 1) enhancement of microglial phagocytosis, 2) enhancement of Abeta efflux from the brain (Abeta sequestration/peripheral sink). Accumulated evidences support both mechanisms are involved in Abeta reduction. Further understanding of mechanism is necessary to identify mechanism-based therapeutic approaches.

Address correspondence to Dr. Yasuji Matsuoka, Department of Neurology, Georgetown University Medical Center (Washington, DC 20057, USA) (Present address: Neurodegeneration Research, GlaxoSmithKline, Shanghai 201203)