Aβ and tau structure-based biomarkers for a blood- and CSF-based two-step recruitment strategy to identify patients with dementia due to Alzheimer's disease

Introduction Alzheimer's disease (AD) diagnosis requires invasive CSF analysis or expensive brain imaging. Therefore, a minimal-invasive reliable and cost-effective blood test is requested to power large clinical AD trials at reduced screening failure. Methods We applied an immuno-infrared sensor to measure the amyloid-beta (A beta) and tau secondary structure distribution in plasma and CSF as structure-based biomarkers for AD (61 disease controls, 39 AD cases). Results Within a first diagnostic screening step, the structure-based A beta blood biomarker supports AD identification with a sensitivity of 90%. In a second diagnostic validation step, the combined use of the structure-based CSF biomarkers A beta and tau excluded false-positive cases which offers an overall specificity of 97%. Discussion The primary A beta -based blood biomarker funnels individuals with suspected AD for subsequent validation of the diagnosis by structure-based combined analysis of the CSF biomarkers A beta and tau. Our novel two-step recruitment strategy substantiates the diagnosis of AD with a likelihood of 29.