Cited by 297Alzheimer's disease research and treatmentsDementia and Cognitive Impairment ResearchNeuroinflammation and Neurodegeneration Mechanisms

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β-Secretase Activity Increases with Aging in Human, Monkey, and Mouse Brain

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Fukumoto, Hiroaki, Rosene, Douglas L., Moss, Mark B., Raju, Susan, Hyman, Bradley T., Irizarry, Michael C.·2004·The American Journal of Pathology

DOI 10.1016/s0002-9440(10)63159-8PMC PMC1602259

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Abstract

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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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.
ORCID: Fukumoto, Hiroaki
Rosene, Douglas L.
Moss, Mark B.
Hyman, Bradley T.
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)
DOI: 10.1016/s0002-9440(10)63159-8
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
Licence: www.elsevier.com/tdm/userlicense/1.0/ (tdm)
www.elsevier.com/legal/tdmrep-license (tdm)
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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β-Secretase Activity Increases with Aging in Human, Monkey, and Mouse Brain

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