Fluid biomarkers of dementia and neurodegeneration: insights into diagnosis and prognosis

The work described in this thesis illustrates the roadmap of novel neuronal biomarker immunoassay development and validation, clinical evaluation, and their potential commercial use. We have discussed the existing bottlenecks in immunoassay standardization and their consequences towards clinical and commercial applications. A primary component of this thesis was the evaluation of synaptic proteins as novel biomarkers of dementia and neurodegeneration. Within our research and that of our colleagues, we identified a shift in the landscape of dementia biomarker research. As such, not only is there a need for specific differential biomarkers for AD and bvFTD, but also early-stage biomarkers that have prognostic potential. Moreover, there is a rising demand for novel neuronal biomarkers in blood, which offers a less invasive matrix than CSF, from clinicians, patients, and IVD companies alike. Building upon the results obtained in our CSF studies, we found a novel synaptic biomarker in plasma, namely SNAP25, that has good prognostic potential in pre-clinical AD. This thesis has also contributed towards generating interest from stakeholders and pharmaceutical companies towards synaptic biomarkers for disease staging and monitoring treatment responses. To conclude, the synaptic biomarkers in CSF and plasma discussed herein have the potential to improve clinical diagnosis of dementias, as well as identify at-risk patient groups at early stages of AD.