Amyloid blood biomarker detects Alzheimer's disease

Alzheimer's disease (AD) is currently incurable, but there is general agreement that a minimally invasive blood biomarker for screening in preclinical stages would be crucial for future therapy. Diagnostic tools for detection of AD are either invasive like cerebrospinal fluid (CSF) biomarkers o...

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Main Authors: Nabers, Andreas (Author) , Saum, Kai-Uwe (Author) , Brenner, Hermann (Author)
Format: Article (Journal)
Language:English
Published: 06.04.2018
In: EMBO molecular medicine
Year: 2018, Volume: 10, Issue: 5
ISSN:1757-4684
DOI:10.15252/emmm.201708763
Online Access:Verlag, kostenfrei, Volltext: http://dx.doi.org/10.15252/emmm.201708763
Verlag, kostenfrei, Volltext: http://embomolmed.embopress.org/content/early/2018/04/04/emmm.201708763
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Author Notes:Andreas Nabers, Laura Perna, Julia Lange, Ute Mons, Jonas Schartner, Jörn Güldenhaupt, Kai-Uwe Saum, Shorena Janelidze, Bernd Holleczek, Dan Rujescu, Oskar Hansson, Klaus Gerwert & Hermann Brenner

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520 |a Alzheimer's disease (AD) is currently incurable, but there is general agreement that a minimally invasive blood biomarker for screening in preclinical stages would be crucial for future therapy. Diagnostic tools for detection of AD are either invasive like cerebrospinal fluid (CSF) biomarkers or expensive such as positron emission tomography (PET) scanning. Here, we determine the secondary structure change of amyloid‐β (Aβ) in human blood. This change used as blood amyloid biomarker indicates prodromal AD and correlates with CSF AD biomarkers and amyloid PET imaging in the cross‐sectional BioFINDER cohort. In a further population‐based longitudinal cohort (ESTHER), the blood biomarker detected AD several years before clinical diagnosis in baseline samples with a positive likelihood ratio of 7.9; that is, those who were diagnosed with AD over the years were 7.9 times more likely to test positive. This assay may open avenues for blood screening of early AD stages as a funnel for further more invasive and expensive tests. Synopsis <img class="highwire-embed" alt="Embedded Image" src="http://embomolmed.embopress.org/sites/default/files/highwire/embomm/early/2018/04/04/emmm.201708763/embed/graphic-1.gif"/> Determination of the amyloid‐β secondary structure distribution in blood plasma by an immuno‐IR‐sensor correlates with PET scanning and CSF markers in Alzheimer's disease (AD) patients, with potentials to be an accurate, simple, and minimally invasive biomarker for early AD detection. The amyloid‐β (Aβ) secondary structure distribution in blood plasma can be directly determined by the secondary structure sensitive amide I band.Prodromal AD cases (BioFINDER study) showed significant correlations between the amide I frequency shift and PET scanning results or CSF biomarker values.Early AD identification (Esther) yielded in 71% sensitivity, 91% specificity, and a LR+ of 7.9-8 years before clinical symptoms appeared, in agreement with the BioFINDER study.The plasma biomarker may be used as a routine minimal‐invasive, low‐cost funnel to pre‐select individuals which should undergo lumbar puncture or PET scanning. 
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