Academic Journal
Characterization of plasma β‐secretase (BACE1) activity and soluble amyloid precursor proteins as potential biomarkers for Alzheimer's disease
| العنوان: | Characterization of plasma β‐secretase (BACE1) activity and soluble amyloid precursor proteins as potential biomarkers for Alzheimer's disease |
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| المؤلفون: | Wu, Guoxin, Sankaranarayanan, Sethu, Wong, Jacky, Tugusheva, Katherine, Michener, Maria S., Shi, Xiaoping, Cook, Jacquelynn J., Simon, Adam J., Savage, Mary J. |
| المصدر: | Journal of Neuroscience Research ; volume 90, issue 12, page 2247-2258 ; ISSN 0360-4012 1097-4547 |
| بيانات النشر: | Wiley |
| سنة النشر: | 2012 |
| المجموعة: | Wiley Online Library (Open Access Articles via Crossref) |
| الوصف: | Reduction in cerebrospinal fluid (CSF) amyloid β42 (Aβ42) and elevation in total tau and phospho‐thr181 tau consistently differentiate between Alzheimer's disease (AD) and age‐matched control subjects. In contrast, CSF β‐site APP‐cleaving enzyme activity (BACE1) and soluble amyloid precursor proteins α and β (sAPPα and sAPPβ) are without consistent patterns in AD subjects. Plasma sampling is much easier, with fewer side effects, and is readily applied in primary care centers, so we have developed and validated novel plasma BACE activity, sAPPβ, and sAPPα assays and investigated their ability to distinguish AD from age‐matched controls. Plasma BACE activity assay was sensitive and specific, with signal being immunodepleted with a specific BACE1 antibody and inhibited with a BACE1‐specific inhibitor. Plasma sAPPβ and sAPPα assays were specific, with signal diluting linearly, immunodepleted with specific antibodies, and at background levels in APP knockout mice. In rhesus monkeys, BACE1 but not γ‐secretase inhibitor led to significant lowering of plasma sAPPβ with concurrent elevation of plasma sAPPα. AD subjects showed a significant increase in plasma BACE1 activity, sAPPβ, sAPPα, and Aβ42 ( P < 0.001) compared with age‐matched controls. In conclusion, plasma BACE activity and sAPP endpoints provide novel investigative biomarkers for AD diagnosis and potential pharmacodynamic biomarkers for secretase inhibitor studies. © 2012 Wiley Periodicals, Inc. |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | English |
| DOI: | 10.1002/jnr.23122 |
| الاتاحة: | http://dx.doi.org/10.1002/jnr.23122 https://api.wiley.com/onlinelibrary/tdm/v1/articles/10.1002%2Fjnr.23122 https://onlinelibrary.wiley.com/doi/pdf/10.1002/jnr.23122 |
| Rights: | http://onlinelibrary.wiley.com/termsAndConditions#vor |
| رقم الانضمام: | edsbas.104B878D |
| قاعدة البيانات: | BASE |
| DOI: | 10.1002/jnr.23122 |
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