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Cited by 496

The DOI matches its Crossref record; 9 of the 9 references it cites were found in a registry or an index.

Amyloid β peptide load is correlated with increased β-secretase activity in sporadic Alzheimer's disease patients

Open access
Li, Rena, Lindholm, Kristina, Yang, Li-Bang, Yue, Xu, Citron, Martin, Yan, Riqiang, Beach, Thomas, Sue, Lucia, Sabbagh, Marwan, Cai, Huaibin, Wong, Philip, Price, Donald, Shen, Yong·2004·Proceedings of the National Academy of Sciences
DOI 10.1073/pnas.0205689101
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Abstract

Whether elevated β-secretase (BACE) activity is related to plaque formation or amyloid β peptide (Aβ) production in Alzheimer's disease (AD) brains remains inconclusive. Here, we report that we used sandwich enzyme-linked immunoabsorbent assay to quantitate various Aβ species in the frontal cortex of AD brains homogenized in 70% formic acid. We found that most of the Aβ species detected in rapidly autopsied brains (<3 h) with sporadic AD were Aβ 1-x and Aβ 1-42, as well as Aβ x-42. To establish a linkage between Aβ levels and BACE, we examined BACE protein, mRNA expression and enzymatic activity in the same brain region of AD brains. We found that both BACE mRNA and protein expression is elevated in vivo in the frontal cortex. The elevation of BACE enzymatic activity in AD is correlated with brain Aβ 1-x and Aβ 1-42 production. To examine whether BACE elevation was due to mutations in the BACE-coding region, we sequenced the entire ORF region of the BACE gene in these same AD and nondemented patients and performed allelic association analysis. We found no mutations in the ORF of the BACE gene. Moreover, we found few changes of BACE protein and mRNA levels in Swedish mutated amyloid precursor protein-transfected cells. These findings demonstrate correlation between Aβ loads and BACE elevation and also suggest that as a consequence, BACE elevation may lead to increased Aβ production and enhanced deposition of amyloid plaques in sporadic AD patients.

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Metadata

Authors
Li, R., Lindholm, K., Yang, L.-B., Yue, X., Citron, M., Yan, R., Beach, T., Sue, L., Sabbagh, M., Cai, H., Wong, P., Price, D., & Shen, Y.
Venue
Proceedings of the National Academy of Sciences
Publisher
Proceedings of the National Academy of Sciences
Published
2004-02-20
Volume
101
Issue
10
Pages
3632-3637
ISSN
  • 0027-8424 (ISSN-L)
  • 1091-6490
DOI
10.1073/pnas.0205689101
OpenAlex
W2033067082
Cited by
496
References
9
FWCI
16.15
Type
journal article
Language
en
Open access
green

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