Affiliations: [a] Department of Cardiothoracic Surgery of the Martin-Luther-University Halle-Wittenberg, Halle, Germany | [b] VA Medical Center, University of California, San Francisco, CA, USA | [c] Clinical Memory Research Unit, Clinical Sciences Malmö, Lund University, Lund, Sweden | [d] University of Goteborg, Sahlgrenska University Hospital, Molndal, Sweden | [e] Department of Psychiatry, Psychosomatic Medicine and Psychotherapy, Goethe University, Frankfurt, Germany
Correspondence:
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Correspondence to: Alexander Navarrete Santos, Department of cardiothoracic surgery of the Martin-Luther-University Halle-Wittenberg, Ernst Grube Str. 40, 06120, Halle, Germany. Tel.: +49 (0)345 5573314; E-mail: [email protected].
Note: [1] These authors contributed equally as senior authors to this work.
Abstract: Oligomers of the amyloid-β peptide (Aβ) are thought to be the most toxic form of Aβ and are linked to the development of Alzheimer's disease (AD). Here, we used a flow cytometric approach for the detection and assessment of oligomers in cerebrospinal fluid (CSF) from AD patients and other neurological disorders. 30 CSF samples from patients suffering from AD (n = 14), non-demented controls (n = 12), and other neurological disorders (dementia with Lewy bodies, n = 2; vascular dementia, n = 1; primary progressive aphasia, n = 1) were analyzed for the presence of Aβ-oligomers by flow cytometry. The CSF levels of total tau (t-tau), phosphorylated tau (p-tau), and amyloid-β (Aβ)42 were determined using ELISA. CSF Aβ-oligomer levels in AD patients were elevated in comparison to the non-AD group (p = 0.073). The ratio Aβ-oligomers/Aβ42 was significantly elevated in AD subjects compared to non-AD subjects (p = 0.001). Most important, there was a negative correlation between the amount of Aβ-oligomers and the Mini-Mental Status Exam score (r = −0.65; p = 0.013) in AD patients. The detection of Aβ-oligomers using flow cytometry analysis seems to be useful in assessing the stage of AD. This is a novel and important finding as none of the currently used CSF biomarkers are clearly associated with dementia severity.
