RT Journal Article
SR Electronic
T1 Blood-Borne Amyloid-β Dimer Correlates with Clinical Markers of Alzheimer's Disease
JF The Journal of Neuroscience
JO J. Neurosci.
FD Society for Neuroscience
SP 6315
OP 6322
DO 10.1523/JNEUROSCI.5180-09.2010
VO 30
IS 18
A1 Victor L. Villemagne
A1 Keyla A. Perez
A1 Kerryn E. Pike
A1 W. Mei Kok
A1 Christopher C. Rowe
A1 Anthony R. White
A1 Pierrick Bourgeat
A1 Olivier Salvado
A1 Justin Bedo
A1 Craig A. Hutton
A1 Noel G. Faux
A1 Colin L. Masters
A1 Kevin J. Barnham
YR 2010
UL http://www.jneurosci.org/content/30/18/6315.abstract
AB Alzheimer's disease (AD) is the most common age-related dementia. Unfortunately due to a lack of validated biomarkers definitive diagnosis relies on the histological demonstration of amyloid-β (Aβ) plaques and tau neurofibrillary tangles. Aβ processing is implicated in AD progression and many therapeutic strategies target various aspects of this biology. While Aβ deposition is the most prominent feature of AD, oligomeric forms of Aβ have been implicated as the toxic species inducing the neuronal dysfunction. Currently there are no methods allowing routine monitoring of levels of such species in living populations. We have used surface enhanced laser desorption ionization time of flight (SELDI-TOF) mass spectrometry incorporating antibody capture to investigate whether the cellular membrane-containing fraction of blood provides a new source of biomarkers. There are significant differences in the mass spectra profiles of AD compared with HC subjects, with significantly higher levels of Aβ monomer and dimer in the blood of AD subjects. Furthermore, levels of these species correlated with clinical markers of AD including brain Aβ burden, cognitive impairment and brain atrophy. These results indicate that fundamental biochemical events relevant to AD can be monitored in blood, and that the species detected may be useful clinical biomarkers for AD.