Alzheimer's disease and blood-brain barrier function-Why have anti-beta-amyloid therapies failed to prevent dementia progression?
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.
Pahnke
Jens
J
University of Rostock, Department of Neurology, Germany. jens.pahnke@med.uni-rostock.de
Walker
Lary C
LC
Scheffler
Katja
K
Krohn
Markus
M
D018528:ATP-Binding Cassette Transporters / Q000378:metabolism; D000544:Alzheimer Disease / Q000453:epidemiology / Q000503:physiopathology* / Q000628:therapy*; D016229:Amyloid beta-Peptides / Q000276:immunology / Q000378:metabolism*; D000818:Animals; D001812:Blood-Brain Barrier / Q000187:drug effects / Q000503:physiopathology*; D017281:Cost of Illness; D018450:Disease Progression; D006801:Humans; D007167:Immunotherapy; D019636:Neurodegenerative Diseases / Q000503:physiopathology; D015995:Prevalence
D018528:ATP-Binding Cassette Transporters; D016229:Amyloid beta-Peptides