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

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

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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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Crossref · 10.1016/s0002-9440(10)63159-8

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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)
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
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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