1. Oligomer antibody development
We have confirmed toxicity of beta amyloid 1-42 oligomers and oligomers of n-truncated beta amyloid with pyroglutamate at position 3 (beta amyloid 3p-42) in cell models. Immunization with beta amyloid 1-42 oligomers resulted in antibodies that could detect oligomers but they were not specific as they also recognised monomers. Immunization with beta amyloid 3p-42 oligomers yielded antibodies that could detect oligomers and low order fibrils, but not monomers. Validation of these antibodies on brain material and in body fluids is ongoing.

2. Assay development
We have developed IPCR and immunoprecipitation assays using oligomer specific antibodies. A polyplex IPCR assay was developed which could measure 2 analytes simultaneously by IPCR probes with different DNA sequences. We have also developed a polyplex IPCR assay, which could measure a range of abeta peptides and tau proteins. The assays are now being validated in cerebrospinal fluid (CSF) samples. We have optimized assays for beta amyloid aggregates based on surface-FIDA, IPCR, and ELISA. The assays are now being validated in AD animal models, brain tissue, or CSF samples.

3. Clinical data collection
We have included 56 controls, 117 subjects with MCI, 108 subjects with AD, and 58 subjects with other dementias. We have established a database with clinical data and we set-up a biobank, which included 5300 CSF samples, 3000 plasma samples, 1900 serum samples, and DNA for 314 subjects. The follow-up of these subjects is ongoing.