Antibody-based therapy in Alzheimer's disease.
BACKGROUND
Alzheimer's disease (AD) is a progressive, age-dependent, neurodegenerative disorder being the most common cause of dementia. The pathological hallmarks are extracellular amyloid-beta (Aβ) deposition and intracellular neurofibrillary tangles containing hyperphosphorylated tau. Stunning results in vaccination trials in transgenic animals led to an antibody-based approach to develop immunotherapeutics for AD. Thus, several monoclonal antibodies raised against Aβ as well as polyclonal antibodies are currently in clinical testing and some of them already entered Phase III clinical trials. New upcoming experimental approaches like antibodies recognizing specific conformational epitopes, single-chain variable fragment antibodies, or intrabodies give hope of further drug development for this incurable disease.


METHODS
The rationale and putative mode of action of antibody-based immunotherapy in AD and delineates correlations for other neurodegenerative diseases. Current clinical trials and recent results of therapeutic antibodies in AD are presented.


CONCLUSIONS
Antibodies against Aβ will not only broaden the therapeutic repertoire but also our knowledge about the pathology in AD. Further results of the clinical trials and new antibody-based approaches will shed light on the importance of Aβ and its removal in AD.
Hannover Medical School, Department of Neurology, Carl-Neuberg-Str. 1, 30625 Hannover, Germany.
Refik
R
Pul
Richard
R
Dodel
Martin
M
Stangel
D000544:Alzheimer Disease / Q000188:drug therapy* / Q000276:immunology; D023582:Alzheimer Vaccines / Q000627:therapeutic use*; D016229:Amyloid beta-Peptides / Q000276:immunology; D000818:Animals; D000906:Antibodies / Q000627:therapeutic use*; D019317:Evidence-Based Medicine; D006801:Humans; D007167:Immunotherapy / Q000379:methods*; D016896:Treatment Outcome; D016875:tau Proteins / Q000276:immunology
D023582:Alzheimer Vaccines; D016229:Amyloid beta-Peptides; D000906:Antibodies; C054369:MAPT protein, human; D016875:tau Proteins