Antibodies against beta-amyloid slow cognitive decline in Alzheimer's disease.
To test whether antibodies against beta-amyloid are effective in slowing progression of Alzheimer's disease, we assessed cognitive functions in 30 patients who received a prime and a booster immunization of aggregated Abeta(42) over a 1 year period in a placebo-controlled, randomized trial. Twenty patients generated antibodies against beta-amyloid, as determined by tissue amyloid plaque immunoreactivity assay. Patients who generated such antibodies showed significantly slower rates of decline of cognitive functions and activities of daily living, as indicated by the Mini Mental State Examination, the Disability Assessment for Dementia, and the Visual Paired Associates Test of delayed recall from the Wechsler Memory Scale, as compared to patients without such antibodies. These beneficial clinical effects were also present in two of three patients who had experienced transient episodes of immunization-related aseptic meningoencephalitis. Our results establish that antibodies against beta-amyloid plaques can slow cognitive decline in patients with Alzheimer's disease.
Hock
Christoph
C
Division of Psychiatry Research, University of Zurich, August Forel Strasse 1, 8008 Zurich, Switzerland. chock@bli.unizh.ch
Konietzko
Uwe
U
Streffer
Johannes R
JR
Tracy
Jay
J
Signorell
Andri
A
Müller-Tillmanns
Britta
B
Lemke
Ulrike
U
Henke
Katharina
K
Moritz
Eva
E
Garcia
Esmeralda
E
Wollmer
M Axel
MA
Umbricht
Daniel
D
de Quervain
Dominique J F
DJ
Hofmann
Marc
M
Maddalena
Alessia
A
Papassotiropoulos
Andreas
A
Nitsch
Roger M
RM
D000203:Activities of Daily Living; D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000276:immunology / Q000473:pathology / Q000628:therapy*; D016229:Amyloid beta-Peptides / Q000032:analysis / Q000276:immunology*; D000818:Animals; D000906:Antibodies / Q000008:administration & dosage / Q000097:blood / Q000134:cerebrospinal fluid; D003071:Cognition; D003072:Cognition Disorders / Q000276:immunology / Q000473:pathology / Q000628:therapy*; D018450:Disease Progression; D005260:Female; D006624:Hippocampus / Q000276:immunology / Q000473:pathology; D006801:Humans; D016233:Immunotherapy, Active; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D008875:Middle Aged; D009483:Neuropsychological Tests; D010352:Patient Dropouts; D010446:Peptide Fragments / Q000032:analysis / Q000276:immunology*; D058225:Plaque, Amyloid / Q000276:immunology / Q000473:pathology; D011237:Predictive Value of Tests; D016896:Treatment Outcome
D016229:Amyloid beta-Peptides; D000906:Antibodies; D010446:Peptide Fragments; C075222:amyloid beta-protein (1-42)