Journal
AMERICAN JOURNAL OF PATHOLOGY
Volume 184, Issue 1, Pages 141-147Publisher
ELSEVIER SCIENCE INC
DOI: 10.1016/j.ajpath.2013.10.002
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Funding
- National Institutes of Health [NIA025888, NIAR01AG032441]
- Alzheimer Association [IIRG-09-61521, IIRG-07-59510]
- American Health Assistance Foundation [G2006-118, A2008-642]
- National Natural Science Foundation of China [81100861]
- Specialized Research Fund for the Doctoral Program of Higher Education [20100071120081]
- National Institute of Neurological Disorders and Stroke from the National Brain and Tissue Resource [U24NS072026]
- National Institute on Aging from the Arizona Alzheimer's Disease Core Center [P30AG19610]
- Arizona Department of Health Services from the Arizona Alzheimer's Research Center [211002]
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We recently discovered elevated B-secretase 1 (BACE1) activity in brains with sporadic Alzheimer disease (AD). Moreover, we also found high Levels of BACE1 enzymatic activity in the cerebrospinal fluid from patients with both mild cognitive impairment (MCI) and AD. These results suggest that elevation of BACE1 enzymatic activity may occur early or may contribute to AD. We therefore examined whether BACE1 enzymatic activity was changed in MCI brains. BACE1 activity and tumor necrosis factor (TNF)-alpha Levels were measured by enzymatic assay and ELISA in the temporal cortex from 18 patients with clinically well-characterized AD, 18 patients with MCI, and 18 healthy controls. We found a significant increase in BACE1 activity and protein Level in brains of MCI and AD patients. Moreover, increased BACE1 activity correlated with plaque numbers and cognition status. We also found an increase in TNF-alpha in MCI brains. In vitro study revealed that TNF-alpha rather than other cytokines can up-regulate BACE1 protein expression. These findings suggest that BACE1 increase occurs early in MCI and is possibly induced by TNF-alpha and that BACE1 enzymatic activity may be important for conversion of MCI to AD.
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