The importance of amyloid beta (Abeta) protein to Alzheimer’s Disease is well documented, with increased deposits of Abeta being linked to the formation of senile plaques in the brain. The protein has several epitopes, and an extensive antibody database has been developed over the years to reflect this.
Amyloid beta peptides are derived from the transmembrane amyloid precursor protein (APP). It is thought that disruptions in the APP processing mechanism lead to production of longer and “stickier” forms of the peptide, such as the toxic cleavage product amyloid beta-42 (AB42). This peptide is widely expressed in the brain tissue of Alzheimer’s patients. Recently, studies have suggested that the majority of AB42 peptide expressed in Alzheimer’s Disease is N-terminal truncated (i.e. shortened at the N-terminal) in a modified pyroglutamate form. Pyroglutamic acid (pGlu) is a rare amino acid derived from cyclised glutamine residues.
Of particular interest are Abeta proteins undergoing posttranslational pGlu formation at position 3 or 11 of the N-terminal, with position 3 being most prevalent. Antibody assays using artificial peptide substrates have suggested that the enzyme glutaminyl cyclase plays an important role in this, catalysing the formation of N-terminal pGlu following amyloidogenic APP processing (i.e. formation of insoluble protein aggregates.) The resultant modified peptides are more hydrophobic, more resistant to degradation and more likely to aggregate than the normal form of the protein.
Alzheimer’s Disease researchers are now focussing much of their attention on the molecular pathways leading to their formation of Abeta pyroglutamate-3 and 11, with the aim of developing a vaccine to combat the illness. Researchers at the Cornell Weill Medical College have discovered that Alzheimer’s patients have low levels of AB42 antibodies compared to healthy individuals, but studies in APP transgenic mice have shown that anti-beta Amyloid can reverse the formation of cerebral AB42 deposits. We at Novus Biologicals recently added several new beta amyloid products to our antibody catalog, including beta Amyloid pyroglutamate 3 and 11 antibodies.
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