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

• Main Authors: Andreas Nabers, Henning Hafermann, Jens Wiltfang, Klaus Gerwert
• Format: Article
• Language: English
• Published: Wiley 2019-12-01
• Series: Alzheimer’s & Dementia: Diagnosis, Assessment & Disease Monitoring
• Subjects: Alzheimer's disease; Amyloid‐beta; Tau; Protein misfolding; Diagnostics
• Online Access: https://doi.org/10.1016/j.dadm.2019.01.008

Abstract 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‐β (Aβ) 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 Aβ 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 Aβ and tau excluded false‐positive cases which offers an overall specificity of 97%. Discussion The primary Aβ‐based blood biomarker funnels individuals with suspected AD for subsequent validation of the diagnosis by structure‐based combined analysis of the CSF biomarkers Aβ and tau. Our novel two‐step recruitment strategy substantiates the diagnosis of AD with a likelihood of 29.