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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.

Author information

1
Department of Biophysics, Ruhr-University Bochum, Bochum, Germany.
2
LVR-Hospital Essen, Department of Psychiatry and Psychotherapy, Faculty of Medicine, University of Duisburg-Essen, Essen, Germany.
3
Department of Psychiatry and Psychotherapy, University Medical Center Goettingen (UMG), Georg-August-University Goettingen, Göttingen, Germany.
4
German Center for Neurodegenrative Diseases (DZNE), Göttingen, Germany.
5
iBiMED, Medical Sciences Department, University of Aveiro, Aveiro, Portugal.

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.

KEYWORDS:

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

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