The DOI matches its Crossref record; 48 of the 50 references it cites were found in a registry or an index.
β-Secretase Activity Increases with Aging in Human, Monkey, and Mouse Brain
Open accessAbstract
Amyloid beta protein (A beta) accumulates in the brains of aging humans, amyloid precursor protein (APP) transgenic mouse lines, and rhesus monkeys. We tested the hypothesis that aging was associated with increased activity of the beta-site amyloid precursor protein cleaving enzyme (beta-secretase, BACE) in brain. We evaluated BACE activity, BACE protein, and formic acid-extractable A beta levels in cohorts of young (4 months old) and old (14 to 18 months old) nontransgenic mice (n = 16) and Tg2576 APP transgenic mice (n = 17), young (4.4 to 12.7 years old) and old (20.9 to 30.4 years old) rhesus monkeys (n = 17), and a wide age range (18 to 92 years old) of nondemented human brains (n = 25). Aging was associated with increased brain A beta levels in each cohort. Furthermore BACE activity increased significantly with age in mouse, monkey, and human brains, independent of brain region. BACE protein levels, however, were unchanged with age. BACE activity correlated with formic acid-extractable A beta levels in transgenic mouse, nontransgenic mouse, and human cortex, but not in monkey brain. These data suggest that an age-related increase of BACE activity contributes to the increased production and accumulation of brain A beta, and potentially predisposes to Alzheimer's disease in humans.
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“Previous studies consistently reported that expression and activity of BACE1 are increased during aging in the brains mice, rats and humans (Boissonneault et al. 2009, Che et al. 2014, Fukumoto et al. 2004, Rossner et al. 2006), raising the possibility of a link between aging-associated alterations in BACE1 and the increased risk for AD.”
From miR‐186 is decreased in aged brain and suppresses BACE 1 expression (2016) · cites this paper as Fukumoto et al. 2004
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Alzheimer's Disease and the Amyloid-β Peptide
Murphy, M. P., & LeVine, H. (2010) · Journal of Alzheimer's Disease · doi:10.3233/jad-2010-1221 · Cited by 1,750
Lim, G. P., Calon, F., Morihara, T., Yang, F., Teter, B., Ubeda, O. J., Salem, N., Frautschy, S. A., & Cole, G. M. (2005) · Journal of Neuroscience · doi:10.1523/jneurosci.4225-04.2005 · Cited by 697
Hypoxia facilitates Alzheimer's disease pathogenesis by up-regulating BACE1 gene expression
Sun, X., He, G., Qing, H., Zhou, W., Dobie, F., Cai, F., Staufenbiel, M., Huang, L. E., & Song, W. (2006) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0606298103 · Cited by 605
The Alzheimer's disease Beta-secretase enzyme, BACE1
Cole, S. L., & Vassar, R. (2007) · Molecular Neurodegeneration · doi:10.1186/1750-1326-2-22 · Cited by 550
Inhibition of GSK3β-mediated BACE1 expression reduces Alzheimer-associated phenotypes
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Metadata
- Authors
- Fukumoto, H., Rosene, D. L., Moss, M. B., Raju, S., Hyman, B. T., & Irizarry, M. C.
- Affiliations
- Massachusetts General Hospital (US)
- Boston University (US)
- Corresponding author
- Irizarry, Michael C.
- Venue
- The American Journal of Pathology
- Publisher
- Elsevier BV
- Published
- 2004-02
- Volume
- 164
- Issue
- 2
- Pages
- 719-725
- ISSN
- 0002-9440 (ISSN-L)
- PMC
- PMC1602259
- OpenAlex
- W2076868543
- Cited by
- 294
- References
- 50
- Citations by year
- 2026: 6 · 2025: 7 · 2024: 11 · 2023: 13 · 2022: 13 · 2021: 11 · 2020: 12 · 2019: 10 · 2018: 10 · 2017: 13 · 2016: 16 · 2015: 16 · 2014: 8 · 2013: 23 · 2012: 18
- FWCI
- 11.75
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- American Journal Of Pathology (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Boston University (RR00165, PHS MH/NS 31862)
- National Institutes of Health (AG05134, AG15453, AG00001)
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Alzheimer's disease research and treatments
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Keywords
- beta-secretase, brain aging, amyloid-beta deposition, amyloid precursor protein, Alzheimer's disease, rhesus monkeys, human brain, cerebral cortex
- MeSH terms
- Aging, Animals, Brain, Enzyme-Linked Immunosorbent Assay, Humans, Macaca mulatta, Mice, Transgenic, Blotting, Western, Amyloid beta-Peptides, Aspartic Acid Endopeptidases, Mice
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