Anti-addl monoclonal antibody and use thereof

Abstract

The present invention relates to antibodies that -differentially -recognize- -multi- dimensional conformations- of- Ass- derived diffusible ligands, also known as ADDLs. The antibodies of the invention can distinguish between Alzheimer's Disease and control human brain extracts and are useful in methods of detecting ADDLs and diagnosing Alzheimer's Disease. The present antibodies also block binding of ADDLs to neurons, assembly of ADDLS, and tau phosphorylation and are there useful in methods for the preventing and treating diseases associated with soluble oligomers of amyloid ss 1-42.

Description

Anti-ADDL monoclonal antibody and its application introduce This application is a continuation-in-part of PCT Application No. PCT / US2005 / 0038125, filed October 21, 2005. Background of the invention Alzheimer's disease is a progressive and degenerative dementia (Terry, et al. (1991) Ann.Neurol.30: 572-580; Coyle (1987) "Encyclopedia of Neuroscience", edited by Adelman , Birkhauser, Boston-Basel-Stuttgart, pp 29-31). In its early stages, Alzheimer's disease is primarily manifested by a profound inability to form new memories (Selkoe (2002) Science 298: 789-791), reportedly due to neurotoxins from amyloid beta (Aβ). Aβ is an amphipathic peptide whose abundance is increased by mutations and risk factors associated with Alzheimer's disease. Fibrils formed from Aβ constitute the core of amyloid plaques, a hallmark of the Alzheimer's brain. Similar filaments produced in vitro are lethal to cultured brain neurons. These findings suggest that memory loss is a consequence of neu...

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Vaccine clinical trials have revealed that people with a strong immune response to the vaccine exhibit cognitive benefits (Hock, et al. (2003) Neuron38: 547-554); however, frequent episodes of CNS inflammation have led to early termination of some trials (Birmingham & Frantz ( 2002) Nat. Med. 8: 199-200)

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