Characterization of Anti-ADDL Antibodies for Use in Tandem LSPR-MALDI Investigation of Alzheimber's Disease Brain ExtractsPublic Deposited
Small, soluble, self-assembling peptide Aβ-oligomers, known as ADDLs (amyloid-derived diffusible ligands), accumulate in the Alzheimer’s disease (AD) brain as Aβ 12-mers and are thought to contribute to AD neuropathological conditions. Unlike plaques, which were once thought to cause neuronal death due to insoluble amyloid plaque deposits, ADDLs initiate abnormal changes in dendritic spine morphology and receptor trafficking, ultimately leading to memory failure. Due to this significant brain impairment caused by AD, there is a great demand for diagnostic techniques to identify the toxic oligomers and assess their interactions with various antibodies. Anti-ADDL antibodies have prevented ADDL toxicity in vitro, and, with the use of dot and Western blots, the antibody with greatest ADDL affinity and specificity has been characterized. This maximum affinity and specificity is necessary for Matrix Assisted Localized Desorption Ionization (MALDI), a mass spectrometry (MS) technique that allows measurement of toxin mass and concentration after identification of the toxic oligomer molecule. Along with the ADDL based bio-barcode, the localized surface plasmon resonance (LSPR) spectroscopy diagnostic assay may allow for a comparison of ADDL concentrations in cerebral spinal fluid (CSF) between control patients and patients with AD symptoms, perhaps acting as a sensor that may lead to earlier therapeutics for AD patients.