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Alzheimers Dement (Amst). 2019 Mar 12;11:257-263. doi: 10.1016/j.dadm.2019.01.008. eCollection 2019 Dec.

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.

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Department of Biophysics, Ruhr-University Bochum, Bochum, Germany.
LVR-Hospital Essen, Department of Psychiatry and Psychotherapy, Faculty of Medicine, University of Duisburg-Essen, Essen, Germany.
Department of Psychiatry and Psychotherapy, University Medical Center Goettingen (UMG), Georg-August-University Goettingen, Göttingen, Germany.
German Center for Neurodegenrative Diseases (DZNE), Göttingen, Germany.
iBiMED, Medical Sciences Department, University of Aveiro, Aveiro, Portugal.



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.


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).


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%.


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.


Alzheimer's disease; Amyloid-beta; Diagnostics; Protein misfolding; Tau

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