Amyloid blood biomarker detects Alzheimer's disease. Issue 5 (6th April 2018)

• Record Type: Journal Article
• Authors: Nabers, Andreas; Perna, Laura; Lange, Julia; Mons, Ute; Schartner, Jonas; Güldenhaupt, Jörn; Saum, Kai‐Uwe; Janelidze, Shorena; Holleczek, Bernd; Rujescu, Dan; Hansson, Oskar; Gerwert, Klaus; Brenner, Hermann
• Is Part Of: EMBO molecular medicine. Volume 10:Issue 5(2018)
• Page Start: n/a
• Page End: n/a
• Publication Date: 2018-04-06
• Subjects: Alzheimer's disease diagnosis -- amyloid‐β in blood plasma -- BioFINDER -- ESTHER -- immuno‐infrared‐sensor; Molecular biology -- Periodicals; Medical genetics -- Periodicals; Pathology, Molecular -- Periodicals; 616.04205
• DOI: 10.15252/emmm.201708763
• Languages: English
• ISSNs: 1757-4676

Abstract

Abstract: 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: 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. Abstract : 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.