Amyloid-β oligomers in cerebrospinal fluid are associated with cognitive decline in patients with Alzheimer's disease.
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.
Department of Cardiothoracic Surgery of the Martin-Luther-University Halle-Wittenberg, Halle, Germany. alexander.navarrete@medizin.unihalle.de
Alexander Navarrete
AN
Santos
Michael
M
Ewers
Lennart
L
Minthon
Andreas
A
Simm
Rolf-Edgar
RE
Silber
Kaj
K
Blennow
David
D
Prvulovic
Oskar
O
Hansson
Harald
H
Hampel
D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000134:cerebrospinal fluid* / Q000175:diagnosis / Q000453:epidemiology; D016229:Amyloid beta-Peptides / Q000134:cerebrospinal fluid*; D015415:Biomarkers / Q000134:cerebrospinal fluid; D016022:Case-Control Studies; D003072:Cognition Disorders / Q000134:cerebrospinal fluid* / Q000175:diagnosis / Q000453:epidemiology; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D010446:Peptide Fragments / Q000134:cerebrospinal fluid
D016229:Amyloid beta-Peptides; D015415:Biomarkers; D010446:Peptide Fragments