TY - JOUR
T1 - A beta 40 Oligomers Identified as a Potential Biomarker for the Diagnosis of Alzheimer's Disease
AU - Gao, Carol Man
AU - Yam, Alice Y.
AU - Wang, Xuemei
AU - Magdangal, Erika
AU - Salisbury, Cleo
AU - Peretz, David
AU - Zuckermann, Ronald N.
AU - Connolly, Michael D.
AU - Hansson, Oskar
AU - Minthon, Lennart
AU - Zetterberg, Henrik
AU - Blennow, Kaj
AU - Fedynyshyn, Joseph P.
AU - Allauzen, Sophie
PY - 2010
Y1 - 2010
N2 - Alzheimer's Disease (AD) is the most prevalent form of dementia worldwide, yet the development of therapeutics has been hampered by the absence of suitable biomarkers to diagnose the disease in its early stages prior to the formation of amyloid plaques and the occurrence of irreversible neuronal damage. Since oligomeric A beta species have been implicated in the pathophysiology of AD, we reasoned that they may correlate with the onset of disease. As such, we have developed a novel misfolded protein assay for the detection of soluble oligomers composed of A beta x-40 and x-42 peptide (hereafter A beta 40 and A beta 42) from cerebrospinal fluid (CSF). Preliminary validation of this assay with 36 clinical samples demonstrated the presence of aggregated A beta 40 in the CSF of AD patients. Together with measurements of total A beta 42, diagnostic sensitivity and specificity greater than 95% and 90%, respectively, were achieved. Although larger sample populations will be needed to confirm this diagnostic sensitivity, our studies demonstrate a sensitive method of detecting circulating A beta 40 oligomers from AD CSF and suggest that these oligomers could be a powerful new biomarker for the early detection of AD.
AB - Alzheimer's Disease (AD) is the most prevalent form of dementia worldwide, yet the development of therapeutics has been hampered by the absence of suitable biomarkers to diagnose the disease in its early stages prior to the formation of amyloid plaques and the occurrence of irreversible neuronal damage. Since oligomeric A beta species have been implicated in the pathophysiology of AD, we reasoned that they may correlate with the onset of disease. As such, we have developed a novel misfolded protein assay for the detection of soluble oligomers composed of A beta x-40 and x-42 peptide (hereafter A beta 40 and A beta 42) from cerebrospinal fluid (CSF). Preliminary validation of this assay with 36 clinical samples demonstrated the presence of aggregated A beta 40 in the CSF of AD patients. Together with measurements of total A beta 42, diagnostic sensitivity and specificity greater than 95% and 90%, respectively, were achieved. Although larger sample populations will be needed to confirm this diagnostic sensitivity, our studies demonstrate a sensitive method of detecting circulating A beta 40 oligomers from AD CSF and suggest that these oligomers could be a powerful new biomarker for the early detection of AD.
U2 - 10.1371/journal.pone.0015725
DO - 10.1371/journal.pone.0015725
M3 - Article
C2 - 21209907
SN - 1932-6203
VL - 5
JO - PLoS ONE
JF - PLoS ONE
IS - 12
ER -