Disease modifying therapies for Alzheimer's disease targeting Aβ oligomers: implications for therapeutic mechanisms.
Several lines of evidence indicate that amyloid β (Aβ), particularly Aβ oligomers (AβOs), plays a causative role in Alzheimer's disease. However, the mechanisms underlying the action of an anti-AβO antibody to clarify the toxic action of AβOs remain elusive. Here, we showed that the anti-AβO antibody (monoclonal 72D9) can modify the Aβ aggregation pathway. We also found that 72D9 directly sequesters both extracellular and intraneuronal AβOs in a nontoxic state. Thus, therapeutic intervention targeting AβOs is a promising strategy for neuronal protection in Alzheimer's disease.
Department of Neurology, Institute of Brain Science, Hirosaki University Graduate School of Medicine, Aomori 036-8562, Japan.
Etsuro
E
Matsubara
Ayumi
A
Takamura
Yasuhide
Y
Okamoto
Hideto
H
Oono
Takashi
T
Nakata
Yasuhito
Y
Wakasaya
Takeshi
T
Kawarabayashi
Mikio
M
Shoji
D000544:Alzheimer Disease / Q000188:drug therapy*; D016229:Amyloid beta-Peptides / Q000037:antagonists & inhibitors* / Q000737:chemistry* / Q000633:toxicity; D000911:Antibodies, Monoclonal / Q000494:pharmacology / Q000627:therapeutic use; D001921:Brain / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D002460:Cell Line; D006801:Humans; D058990:Molecular Targeted Therapy; D020836:Protein Structure, Quaternary
D016229:Amyloid beta-Peptides; D000911:Antibodies, Monoclonal