Abstract
AD is characterized as a protein misfolding disease due to the accumulation of abnormally folded amyloid beta protein and also considered a tauopathy. However, several proteins are involved in the pathogenesis and diagnosis of neurodegenerative disorders like AD. Some of these biomarkers are only available in lowest concentrations in CSF and/or blood samples during the early-stage of the disorders; other could only be detected in biopsies samples. Furthermore the sample size for testing is a critical issue. We addressed these challenges by improving immunoassays for different biomarkers. Immuno-PCR first described by Sano et al. is a highly promising technique for the ultrasensitive analysis of proteins, like biomarkers, biopharmaceutical compounds, therapeutic antibodies, cytokines and many more. Immuno-PCR combines the well-established ELISA methodology with the signal amplification power of the PCR. As a consequence Immuno-PCR does not lead only to an about 100 to 10,000-fold gain in sensitivity compared to conventional ELISA. It also reveals a set of additional advantages. We show the high sensitive detection of different Alzheimer's disease (AD) related biomarkers, e.g. phosphorylated TAU. Additionally, we could decrease the needed sample volume to only some microliter still showing an improved sensitivity compared to standard immunoassays. These results show ways for improved detection and prognosis of CNS biomarkers in AD and related dementias, including parkinsonian movement disorders, and ways for future developments.
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