Journal
ALZHEIMER'S & DEMENTIA: DIAGNOSIS, ASSESSMENT & DISEASE MONITORING
Volume 11, Issue 1, Pages 257-263Publisher
WILEY
DOI: 10.1016/j.dadm.2019.01.008
Keywords
Alzheimer's disease; Amyloid-beta; Tau; Protein misfolding; Diagnostics
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Funding
- Ilidio Pinho professorship
- iBiMED [UID/BIM/04501/2013]
- FCT at the University of Aveiro, Portugal [PTDC/DTP_PIC/5587/2014]
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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.
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