Alzheimer's disease and blood-brain barrier function-Why have anti-β-amyloid therapies failed to prevent dementia progression?

NEUROSCIENCE AND BIOBEHAVIORAL REVIEWS

卷:33

Review

Pahnke, Jens¹  Walker, Lary C.^2,3  Scheffler, Katja¹  Krohn, Markus¹ 

[1] Univ Rostock, Dept Neurol, NRL, D-18147 Rostock, Germany

[2] Emory Univ, Yerkes Natl Primate Res Ctr, Atlanta, GA 30322 USA

[3] Emory Univ, Dept Neurol, Atlanta, GA 30322 USA

关键词: ABC transporter;    Alzheimer's disease;    Oligomers;    Neurodegeneration;    MDR1;    ABCB1;    MRP1;    ABCC1;    BCRP;    ABCG2;    Dementia;    Abeta;    Blood-brain barrier;    P-glycoprotein;    Immunization;   

DOI  :  10.1016/j.neubiorev.2009.05.006

来源: Elsevier

【 摘 要 】

Proteopathies of the brain are defined by abnormal, disease-inducing protein deposition that leads to functional abrogation and death of neurons. Immunization trials targeting the removal of amyloid-beta plaques in Alzheimer's disease have so far failed to stop the progression of dementia, despite autopsy findings of reduced plaque load. Here, we summarize current knowledge of the relationship between AD pathology and blood-brain barrier function, and propose that the activation of the excretion function of the blood-brain barrier might help to achieve better results in trials targeting the dissolution of cerebral amyloid-beta aggregates. We further discuss a possible role of oligomers in limiting the efficacy of immunotherapy. (C) 2009 Elsevier Ltd. All rights reserved.

【 授权许可】

Free