کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
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5624255 | 1406242 | 2015 | 9 صفحه PDF | دانلود رایگان |
BackgroundProteins pathogenic in Alzheimer's disease (AD) were extracted from neurally derived blood exosomes and quantified to develop biomarkers for the staging of sporadic AD.MethodsBlood exosomes obtained at one time-point from patients with AD (n = 57) or frontotemporal dementia (FTD) (n = 16), and at two time-points from others (n = 24) when cognitively normal and 1 to 10 years later when diagnosed with AD were enriched for neural sources by immunoabsorption. AD-pathogenic exosomal proteins were extracted and quantified by enzyme-linked immunosorbent assays.ResultsMean exosomal levels of total tau, P-T181-tau, P-S396-tau, and amyloid β 1-42 (Aβ1-42) for AD and levels of P-T181-tau and Aβ1-42 for FTD were significantly higher than for case-controls. Step-wise discriminant modeling incorporated P-T181-tau, P-S396-tau, and Aβ1-42 in AD, but only P-T181-tau in FTD. Classification of 96.4% of AD patients and 87.5% of FTD patients was correct. In 24 AD patients, exosomal levels of P-S396-tau, P-T181-tau, and Aβ1-42 were significantly higher than for controls both 1 to 10 years before and when diagnosed with AD.ConclusionsLevels of P-S396-tau, P-T181-tau, and Aβ1-42 in extracts of neurally derived blood exosomes predict the development of AD up to 10 years before clinical onset.
Journal: Alzheimer's & Dementia - Volume 11, Issue 6, June 2015, Pages 600-607.e1