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- W2104906906 abstract "Unfortunately definitive diagnosis of Alzheimer's disease (AD) relies on post-mortem histological demonstration of amyloid-β (Aβ) plaques and tau neurofibrillary tangles. Aβ processing has been implicated in AD progression and many therapeutic strategies targeting various aspects of this biology under clinical investigation. However a lack of validated biomarkers has hampered the efficient design of appropriate trials. While Aβ deposition is the most prominent feature of AD, recent studies have implicated oligomeric forms of Aβ as the toxic species that induce the neuronal dysfunction associated with AD. These species include synaptotoxic Aβ dimers isolated from post mortem AD brain tissue. Currently there are no methods allowing routine monitoring of levels of such species in living populations. To determine whether oligomeric forms of Aβ can be identified in blood and if so do levels of the oligomers differ between healthy controls and diseased subjects. The blood of 43 AD, 23 mild cognitively impaired (MCI) and 52 healthy control (HC) subjects was analysed for the presence of APP/Aβ species by Surface Enhanced Laser Desorption Ionization Time of Flight (SELDI-TOF) mass spectrometry incorporating antibody capture. There are significant differences in the mass spectra profiles of the blood fractions from AD compared with HC subjects. These differences were consistent with there being two distinct processing pathways for APP with an amyloidogenic pathway favored in AD. This resulted in significantly higher levels of Aβ monomer and Aβ dimer in the blood of AD subjects with respectively 16% and 35% increases in the levels of these species over controls. Furthermore levels of these species correlated with clinical markers of AD including Mini-Mental State Examination scores, memory impairment and brain Aβ burden as determined by 11C-PiB PET imaging. These results indicate that fundamental biochemical events relevant to AD such as Aβ generation and aggregation can be monitored in blood, and that the species detected may be useful clinical biomarkers for AD." @default.
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- W2104906906 date "2009-07-01" @default.
- W2104906906 modified "2023-10-18" @default.
- W2104906906 title "O1-06-05: Blood Borne Aβ Dimer Correlates With Clinical Markers of Alzheimer's Disease" @default.
- W2104906906 doi "https://doi.org/10.1016/j.jalz.2009.07.123" @default.
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