Blood-Borne Amyloid- Dimer Correlates with Clinical Markers of Alzheimer's Disease
ABSTRACT 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-beta (Abeta) plaques and tau neurofibrillary tangles. Abeta processing is implicated in AD progression and many therapeutic strategies target various aspects of this biology. While Abeta deposition is the most prominent feature of AD, oligomeric forms of Abeta 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 Abeta monomer and dimer in the blood of AD subjects. Furthermore, levels of these species correlated with clinical markers of AD including brain Abeta 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.
- SourceAvailable from: Colin L Masters[Show abstract] [Hide abstract]
ABSTRACT: Progressive cerebral deposition of the amyloid β-protein (Aβ) in brain regions serving memory and cognition is an invariant and defining feature of Alzheimer disease. A highly similar but less robust process accompanies brain aging in many nondemented humans, lower primates, and some other mammals. The discovery of Aβ as the subunit of the amyloid fibrils in meningocerebral blood vessels and parenchymal plaques has led to innumerable studies of its biochemistry and potential cytotoxic properties. Here we will review the discovery of Aβ, numerous aspects of its complex biochemistry, and current attempts to understand how a range of Aβ assemblies, including soluble oligomers and insoluble fibrils, may precipitate and promote neuronal and glial alterations that underlie the development of dementia. Although the role of Aβ as a key molecular factor in the etiology of Alzheimer disease remains controversial, clinical trials of amyloid-lowering agents, reviewed elsewhere in this book, are poised to resolve the question of its pathogenic primacy.Cold Spring Harbor Perspectives in Medicine 06/2012; 2(6):a006262. DOI:10.1101/cshperspect.a006262 · 7.56 Impact Factor
- [Show abstract] [Hide abstract]
ABSTRACT: Alzheimer’s disease is becoming a serious concern in the medical field due to its severity and prevalence. This multifactorial disease manifested by various genetic and nongenetic factors makes its treatment very difficult. Due to the inefficacy of the currently available drugs, newer therapeutic strategies are increasingly in demand. Most of the current drug discovery initiatives are pivoted around amyloid pathology which is considered to be central to the disease progression. In this work, we propose the use of amyloid-binding aptamer conjugated to poly(lactic-co-glycolic acid) (PLGA)-coated curcumin nanoparticles to bind to the amyloid plaques. Curcumin is a plant-derived compound with reported anti-amyloid activity. Recent reports reveal the importance of plasma amyloid in Alzheimer development. We propose that the amyloid-binding aptamer attached curcumin–PLGA nanoparticles can be used as a potential tool in targeting the plasma amyloid and thus helps in Alzheimer therapy.06/2012; 2(2). DOI:10.1007/s12668-012-0040-y
- [Show abstract] [Hide abstract]
ABSTRACT: This paper proposes a new evaluation method using mutual information for radar return signals. It is shown that there is an optimum threshold level for detecting a radar target in the received signal due to the maximization of the mutual information applied to the evaluation methodRadar Conference, 2000. The Record of the IEEE 2000 International; 02/2000