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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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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
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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