A brief look at a some beta-amyloid antibodies

An anti-amyloid immunotherapy aims to use the body’s own immune response to remove the proteins. There are two sorts of vaccines, there are the active and passive vaccines. The active sort injects an exogenous compound that provokes an immune response against beta-amyloid. This was the earlier sort of treatment that caused the bad side effects (e.g., meningoencephalitis caused by Elan’s AN-1792) in trials. The passive sort injects the antibody directly into the body and so does not rely on developing a self immune response. This way better controls the dose of antibody in the body but the exogenous antibody dose needs to be maintained. 

A large list of beta-amyloid antibodies can be found on the Alzforum.org website: http://www.alzforum.org/res/com/ant/default.asp?antigenID=5

Passive antibodies bind to different regions of the beta-amyloid protein for example, some bind to the N-terminal regions and others bind to the central regions.  

Bard et al., 2000 (Elan Pharmaceuticals) studied effects of a N-terminal binding antibody (10D5) and a polyclonal immunoglobulin (Ig) fraction on beta-amyloid levels in mice. The polyclonal immunoglobulin (Ig) fraction reduced plaque burden by 93% and the monoclonal antibody (10D5) reduced plaque burden by 81%. Mice did not demonstrate a T-cell proliferative response to beta-amyloid.

DeMattos et al., (2001) studied the m266 antibody which is directed towards the central region of beta-amyloid. 4 month old PDAPP mice were treated with m266 up to 9 months of age and beta-amyloid deposition was determined by quantitative immunostaining. Briefly, mice treated with the m266 antibody had reduce beta-amyloid levels compared to those treated with PBS or IgG. It was proposed that m266 antibody could act as a ‘beta-amyloid sink’. The antibody could bind to beta-amyloid in the bloodstream and cause a shift in the equilibrium and create a “peripheral sink” (DeMatos et al., 2001, Lemere et al., 2003).

The reduction of beta-amyloid plaques is more efficient when the administration of anti-amyloid antibodies is directly into the brain rather than into the bloodstream (Thakker et al., 2009; Kotilinek et al., 2002). High doses are needed in the periphery because of the low penetration of the antibody across the blood-brain-barrier. Intracerebroventricular injection of anti-amyloid antibodies is able to reduce impairment of synaptic plasticity in the hippocampus (Klyubin et al., 2005), and also reverse the memory deficit in a transgenic Alzheimer’s mouse model (Billings et al., 2005). Jordao et al., 2010 delivered an anti-amyloid antibody (BAM-10, available from Sigma) to the brain using magnetic resonance imaging-guided focused ultrasound and showed reduced plaque pathology. Chauhan et al., (2011) compared how binding antibody to wheat germ protein improves the treatment in an Alzheimer’s mouse model through intranasal administration. 




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