High activities of BACE1 in brains with mild cognitive impairment

The American Journal of Pathology
Xin ChengYong Shen

Abstract

We recently discovered elevated β-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)-α 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-α in MCI brains. In vitro study revealed that TNF-α 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-α and that BACE1 enzymatic activity may be important for conversion of MCI to AD.

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Citations

Jan 15, 2014·Molecular and Cellular Endocrinology·Rena LiYong Shen
Oct 11, 2015·Journal of Molecular and Cellular Cardiology·Marianne AgstenTobias Huth
Mar 30, 2016·BioDrugs : Clinical Immunotherapeutics, Biopharmaceuticals and Gene Therapy·Genevieve Evin
Apr 10, 2015·Journal of Alzheimer's Disease : JAD·Hao WuQuan-Hong Ma
Mar 23, 2017·Biochemistry. Biokhimii︠a︡·T V AndreevaE I Rogaev
Apr 3, 2019·Protein & Cell·Xiaojuan HeUNKNOWN Major Program Expert Group
Nov 10, 2018·Current Alzheimer Research·Prapimpun WongchitratPiyarat Govitrapong
Mar 14, 2020·Clinical Science·Miroslava KacířováLenka Maletínská
Jun 17, 2020·Alzheimer's & Dementia : the Journal of the Alzheimer's Association·Danlei BiYong Shen
Sep 1, 2020·Acta Neuropathologica·Nils KorteDavid Attwell
Aug 7, 2017·Biomedical Reports·Mohan GiriJayanti Chamling Rai
Jul 11, 2020·Molecular Biology Reports·Parisa AzadfarPejman Mortazavi
Jan 5, 2021·Journal of Biochemical and Molecular Toxicology·Tauqeerunnisa Syeda, Jason R Cannon
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Mar 9, 2021·Neurochemical Research·Dong Xian-HuiGao Wei-Juan
Jul 21, 2021·Journal of Neurogenetics·Owen Davis SandersJayalekshmi Archa Rajagopal
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Sep 18, 2021·Journal of Neurochemistry·Giovanni ZulianiCarlo Cervellati

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