Peripheral administration of a humanized anti-PrP antibody blocks Alzheimer's disease Aβ synaptotoxicity.
Alzheimer's disease (AD) is associated with pathological assembly states of amyloid-β protein (Aβ). Aβ-related synaptotoxicity can be blocked by anti-prion protein (PrP) antibodies, potentially allowing therapeutic targeting of this aspect of AD neuropathogenesis. Here, we show that intravascular administration of a high-affinity humanized anti-PrP antibody to rats can prevent the plasticity-disrupting effects induced by exposure to soluble AD brain extract. These results provide an in vivo proof of principle for such a therapeutic strategy.
Department of Pharmacology and Therapeutics and Institute of Neuroscience, Trinity College, Dublin 2, Republic of Ireland, Medical Research Council Prion Unit and Department of Neurodegenerative Disease, UCL Institute of Neurology, London WC1N 3BG, United Kingdom, Laboratory for Neurodegenerative Research, Center for Neurologic Diseases, Brigham & Women's Hospital, Harvard Institute of Medicine, Boston, Massachusetts 02115, and Biotherapeutics Group, Medical Research Council Technology, Mill Hill, London, United Kingdom NW7 1AD.
Igor
I
Klyubin
Andrew J
AJ
Nicoll
Azadeh
A
Khalili-Shirazi
Michael
M
Farmer
Stephanie
S
Canning
Alexandra
A
Mably
Jacqueline
J
Linehan
Alexander
A
Brown
Madeleine
M
Wakeling
Sebastian
S
Brandner
Dominic M
DM
Walsh
Michael J
MJ
Rowan
John
J
Collinge
D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000473:pathology*; D016229:Amyloid beta-Peptides / Q000494:pharmacology*; D000704:Analysis of Variance; D000818:Animals; D000911:Antibodies, Monoclonal / Q000008:administration & dosage*; D001703:Biophysics; D056547:CA1 Region, Hippocampal / Q000187:drug effects*; D004333:Drug Administration Routes; D004558:Electric Stimulation; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D017774:Long-Term Potentiation / Q000187:drug effects*; D008297:Male; D010446:Peptide Fragments / Q000494:pharmacology*; D011328:Prions / Q000276:immunology* / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D013702:Temporal Lobe / Q000737:chemistry / Q000378:metabolism
D016229:Amyloid beta-Peptides; D000911:Antibodies, Monoclonal; D010446:Peptide Fragments; D011328:Prions; C075222:amyloid beta-protein (1-42)
Alzheimer's; drug discovery; immunotherapy; long-term potentiation; prion